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CAS No. : | 477-47-4 | MDL No. : | MFCD01742647 |
Formula : | C22H22O8 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | YJGVMLPVUAXIQN-HAEOHBJNSA-N |
M.W : | 414.41 | Pubchem ID : | 72435 |
Synonyms : |
Picropodophyllotoxin;AXL1717;NSC 36407;PPP
|
Chemical Name : | (5R,5aS,8aR,9R)-9-Hydroxy-5-(3,4,5-trimethoxyphenyl)-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(5aH)-one |
Num. heavy atoms : | 30 |
Num. arom. heavy atoms : | 12 |
Fraction Csp3 : | 0.41 |
Num. rotatable bonds : | 4 |
Num. H-bond acceptors : | 8.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 103.85 |
TPSA : | 92.68 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | Yes |
CYP3A4 inhibitor : | Yes |
Log Kp (skin permeation) : | -7.4 cm/s |
Log Po/w (iLOGP) : | 3.2 |
Log Po/w (XLOGP3) : | 2.01 |
Log Po/w (WLOGP) : | 2.08 |
Log Po/w (MLOGP) : | 1.43 |
Log Po/w (SILICOS-IT) : | 2.9 |
Consensus Log Po/w : | 2.32 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.71 |
Solubility : | 0.0812 mg/ml ; 0.000196 mol/l |
Class : | Soluble |
Log S (Ali) : | -3.58 |
Solubility : | 0.108 mg/ml ; 0.000261 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -4.75 |
Solubility : | 0.00734 mg/ml ; 0.0000177 mol/l |
Class : | Moderately soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 4.64 |
Signal Word: | Danger | Class: | 6.1 |
Precautionary Statements: | P261-P280-P301+P310-P305+P351+P338 | UN#: | 3462 |
Hazard Statements: | H301-H312-H315-H319-H335 | Packing Group: | Ⅱ |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With methanol; diethyl ether; acetone |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; acetone |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine | ||
With sodium acetate | ||
With pyridine at 60℃; for 1h; | 1 Example 1 (5R,5aR,8aS.9R)-8-oxo-9-(3.4.5-trimethoxyphenyl)-5,5a.6.8.8a.9- 6Χ3νΓθυΓθΓ3'.4':6.7η3ρΗΜοΓ2.3-Γ1.3οχο[-5-νΙ acetate Example 1 (5R,5aR,8aS.9R)-8-oxo-9-(3.4.5-trimethoxyphenyl)-5,5a.6.8.8a.9- 6Χ3νΓθυΓθΓ3'.4':6.7η3ρΗΜοΓ2.3-Γ1.3οχο[-5-νΙ acetate PPP (21 mg, 0.05 mmol) was mixed with pyridine (0.12 mL) and acetic anhydride (0.047 mL). The mixture was heated to 60 °C and stirred for 1 hour. Then methanol (2 mL) was added and precipitate was formed. The mixture was concentrated under reduced pressure and the residue was suspended in ethyl acetate and washed with hydrochloric acid (1 M aq), water and NaHC03 (sat). The organic phase was dried over Na2S04, filtered and evaporated to give the product (21 mg) in 92% yield. The organic phase was dried over Na2S04, filtered and evaporated to give the product (21 mg) in 92% yield and 90% purity according to LCMS (ACE 3 C8, 50 x 3.0 mm, 10% to 97% acetonitrile in 3 min in 0.1% TFA in water, 1 mL/min), MS ESI+ m/z 397, rt 2.112 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With palladium at 240℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With Amberlyst In acetic anhydride for 0.5h; Heating; | |
With sulfuric acid; acetic anhydride | ||
With phosphorus trichloride; benzene |
With hydrogenchloride; acetic acid | ||
With chloroform; phosphorus pentachloride |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With pyridine; chromium(VI) oxide In dichloromethane at 20℃; for 3h; | |
With manganese(IV) oxide; chloroform | ||
In dimethyl sulfoxide for 72h; Forsythia intermedia; Yield given; |
With chromium(VI) oxide In pyridine for 3h; Ambient temperature; Yield given; | ||
With manganese(IV) oxide | ||
162 mg | With chromium(VI) oxide In pyridine Ambient temperature; | |
200 mg | With dipyridinium dichromate In dichloromethane for 3h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ethanol; sulfuric acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With potassium hydroxide In methanol for 0.5h; Ambient temperature; | |
90% | With potassium hydroxide In methanol for 1h; Ambient temperature; | |
78% | With sodium acetate In ethanol; water for 12h; Heating; |
73% | With sodium acetate In ethanol; water for 15h; Reflux; | |
72% | With sodium acetate In ethanol; water at 80℃; for 18h; | |
69% | With sodium acetate In ethanol; water for 15.5h; Reflux; | Synthesis of picropodophyllotoxin (1c) A mixture of1a(2.072 g, 5.0 mmol), absolute ethanol (31 mL), and 10% aq. CH3CO2Na (21 mL) was refluxed. When the reaction was complete for 15.5 h checked by TLC analysis, the mixture was cooled to 0oC and filtered to give the solid, which was recrystallized from absolute ethanol to afford1c(1.419 g, 69% yield). CAS: 1370530-62-3. White solid, m.p. 222-223oC.[α]20D= +5 (c3.2 mg/mL, CHCl3).1H NMR (500 MHz, DMSO-d6)δ: 7.06 (s, 1H, H-5), 6.60 (s, 2H, H-2′, 6′), 6.00 (s, 1H, H-8), 5.91-5.95 (m, 3H, H-4 and OCH2O), 4.51 (d,J= 9.0 Hz, 1H, H-1), 4.34-4.41 (m, 2H, H-11), 3.92 (d,J= 7.5 Hz, 1H, H-2), 3.74 (s, 6H, 3′, 5′-OCH3), 3.69 (s, 3H, 4′-OCH3), 3.40-3.44 (m, 1H, H-3).13C NMR (125 MHz, DMSO-d6)δ: 177.9, 152.8, 145.7, 145.6, 138.3, 136.1, 134.7, 131.4, 107.2, 106.3, 104.4, 100.6, 69.2, 67.2, 59.9, 55.8, 43.6, 43.2, 42.7. MS (ESI-TRAP),m/z(%): 432 ([M+NH4]+, 100). |
With ethanol; sodium acetate | ||
With methanol; palladium | ||
With piperidine; methanol | ||
With sodium hydroxide In chloroform for 12h; | ||
394 mg | With potassium hydroxide In methanol for 4h; Ambient temperature; | |
With borate buffer In 1,4-dioxane; water at 37℃; pH = 10; ionic strength 0.2; | ||
Multi-step reaction with 2 steps 1: 68 percent / PCC / CH2Cl2 / 6 h / Ambient temperature; other reagent 2: 98 percent / NaBH4 / 0 °C | ||
With sodium acetate In ethanol; water for 12h; Heating / reflux; | Picropodophyllin and deoxypicropodophyllin are then prepared from purified podophyllotoxin and deoxypodophyllotoxin, respectively, using essentially identical procedures. Picropodophyllin was dissolved in 70% aqueous ethanol. To the solution was added sodium acetate and the mixture was then refluxed and stirred for 12 h. The mixture was cooled and filtered. The product (precipitate) was washed with ethyl acetate, and then purified by recrystallization from absolute ethanol essentially as described by 0 Buchardt et al . (J Pharmaceut Sci 1986; 75 : 1076-1080) or purified by chromatography on silica gel, mobile phase: hexane-ethyl acetate mixtures, and/or octadecylsilane-bonded silica, mobile phase: aqueous methanol | |
With sodium acetate In ethanol; water |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With lithium tri(t-butoxy)aluminum hydride In tetrahydrofuran for 3.5h; Ambient temperature; | |
80.4% | Stage #1: (5aR,8aS,9R)-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxole-5,8-dione With methanol; sodium tetrahydroborate at 0 - 20℃; Stage #2: With ammonium acetate In water | 6 Example 6Synthesis of Picropodophyllin, i.e. (11 S 5R)-16-hydroxy-10-(3A5-trimethoxyphenyl)- 4.6.13- trioxatetracvclor7.7.0.0A(3, 7).0A{ 11 , 15)1hexadeca- 1.3i7).8-trien-12-one(1 1 R,15S)-16-(3,4,5-trimethoxyphenyl)-4,6,13-trioxatetracyclo-[7.7.0.0A{3,7}.0A{1 1 ,15}]hexadeca- 1 .3(7),8-triene-10,14-dione obtained in analogy with Example 5 (40 g, 97.09 mmol) was suspended in methanol (700 mL) and the resulting mixture cooled to 0 °C. Sodium borohydride (7.39 g, 194.18 mmol) was added in portions over 2 h and the resulting mixture stirred at r.t. overnight. Aqueous ammonium acetate (1 M, 200 mL) was added and the formed precipitate collected by filtration. The filter-cake was washed with 50 vol-% methanol in water (4 x 50 mL) and dried to constant weight under vacuum overnight to give a solid. The mother liquid was ectracted with dichloromethane (3 x 500 mL); the organic solution was washed with brine and dried over anhydrous sodium sulfate. After filtration and concentration, the residue was combined with the dried solid and recrystallized from dichloromethane and hexane to afford a white solid (32.3 g). Yield: 80.4% LCMS ACE 3 C8, 50 x 3.0 mm, 10%-97% acetonitrile in 0.1 % TFA in water, 1 mL/min showed 97% chromatographic purity, MS [M+NH4]+ 432 (100), [M-OH]+ 3971H-NMR (400 MHz, DMSO-d6): δ [ppm] = 2.50-2.58 (m, 1 H, overlapping with solvent residue signal), 3.42 (dd, 1 H), 3.70 (s, 3H), 3.76 (s, 6H), 3.92 (d, 1 H), 3.98 (bs, 1 H), 4.36 (d, 1 H), 4.41 (dd, 1 H), 4.51 (dd, 1 H), 5.42 (app. d, 2H), 6.03 (s, 1 H), 6.50 (s, 2H), 7.08 (s, 1 H) Specific rotation: [a]28D (c = 0.27 in chloroform) +13.0° |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 34% 2: 52% | With Amberlyst for 2h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With 2,6-dimethylpyridine In dichloromethane at 0℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With thionyl chloride In chloroform for 0.166667h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With lithium aluminium tetrahydride In diethyl ether Ambient temperature; | |
With lithium aluminium tetrahydride In diethyl ether at 20℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With sodium tetrahydroborate at 0℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 65% 2: 8% | With magnesium bromide In diethyl ether; benzene at 0 - 20℃; for 11h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; acetic acid Erhitzen des Reaktionsprodukts mit wss. Aceton und Calciumcarbonat; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid for 1h; | Briefly, picropodophyllin was first converted to tetrahydropyranyl- picropodophyllin. Picropodophyllin was dissolved in the reagent dihydropyran plus some small crystals of p-toluenesulfonic acid monohydrate and the mixture was stirred for Ih. A 3% aqueous bicarbonate solution was then added, the volatiles removed in vacuo, and the residue (containing tetrahydropyranylpicropodo- phyllin) was then extracted with diethyl ether and washed.The recovered tetrahydropyranylpicropodophyllin was then reduced to tetrahydropyranylpicropodophyllol . Tetrahydropyranylpicropodo- phyllin was dissolved in dry diethyl ether and lithium aluminum hydride was added. After 3.5 h of of stirring at room temperature, the mixture was cooled to O0C and then carefully treated with water. The produced tetrahydropyranylpicropodophyllol was then extracted by ethyl acetate and washed with water and dried. The recovered tetrahydropyranylpicropodophyllol was then converted to tetrahydropyranylanhydropicropodophyllol by dissolving the former in pyridine and then adding p-toluenesulfonyl chloride in pyridine. The mixture was allowed to react for 4.5 h without contact with air and then some extra of p-toluenesulfonyl chloride was added and the reaction was allowed to proceed for another 4.5 h. The product tetrahydropyranylanhydropicropodophyllol was then extracted with ethyl acetate from the water phase and dried. Tetrahydro- pyranylanhydropicropodophyllol was hydrolyzed to anhydropicro- podophyllol by dissolving the former in ethanol acidified with concentrated HCl and allowing the mixture to stand 1 h in room temperature. After neutralization with aqueous sodium bicarbonate, anhydropicropodophyllol was extracted with ethyl acetate and dried |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 1H-imidazole In N,N-dimethyl-formamide at 20℃; | An alternative method for the synthesis of anhydropicropodophyllol was also tested, and this method gave higher yields of the compound than the method described above. Briefly, the tert- butyldimethylsilyl ether of picropodophyllin was first prepared by adding tert-butyldimethylsilyl (t-BDMS) chloride under N2 to a mixture of picropodophyllin and imidazole in dimethylformamide. The yellow solution was stirred overnight at room temperature and poured into water. The derivative was purified prior to reduction of the lactone group with lithium aluminum hydride in tetrahydrofuran. The latter mixture was then stirred at room temperature for 3 hours yielding the t-BDMS derivative of picropodophyllol (having two free hydroxyl groups) . To a solution of this compound in dichloromethane was added triphenylphosphine and diethyl azodicarboxylate and the mixture was then stirred at room temperature for 3 hours. The solvent was evaporated and the crude t-BDMS ether of anhydropicropodophyllol was then purified.Underivatized anhydropicropodophyllol was obtained by adding tetrabutyl ammonium fluoride to a solution of the derivative in tetrahydrofuran. The mixture was then stirred at room temperature over night. After purification, free and pure anhydropicropodo- phyllol was obtained as a white solid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: LiAlH4 / diethyl ether / 3 h / 20 °C 2: aq. HCl / CHCl3 / 1 h / Heating | ||
Multi-step reaction with 2 steps 1: 80 percent / LAH / diethyl ether / Ambient temperature 2: 88 percent / HClaq. / CHCl3 / 1 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: LiAlH4 / diethyl ether / 3 h / 20 °C 2: aq. HCl / CHCl3 / 1 h / Heating 3: (COCl)2; DMSO; Et3N / CH2Cl2 / 1.5 h / -55 - 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 18 steps 1.1: 61 percent / n-BuLi / tetrahydrofuran; hexane / 2 h / -78 - 20 °C 2.1: 83 percent / NaBH4 / ethanol / 20 °C 3.1: 90 percent / acetic acid / 2 h / 80 °C 4.1: 99 percent / H2 / 10percent Pd/C / ethyl acetate / 6 h / 2482.38 Torr 5.1: 82 percent / LiAlH4 / diethyl ether / 24 h / Heating 6.1: 100 percent / DMAP / pyridine / 16 h / 20 °C 7.1: 66 percent / PPL / dimethylsulfoxide; aq. phosphate buffer / 2.5 h / 20 °C / pH 7.8 8.1: 100 percent / imidazole / dimethylformamide / 7 h / 20 °C 9.1: 100 percent / K2CO3 / methanol / 1.5 h / 20 °C 10.1: 100 percent / oxalyl chloride; DMSO; Et3N / CH2Cl2 / -78 - -40 °C 11.1: 90 percent / NaOMe / methanol / 20 °C 12.1: 93 percent / i-Pr2NEt / CH2Cl2 / 0 - 20 °C 13.1: 95 percent / 2-methyl-2-butene; NaClO2; NaH2PO4 / 2-methyl-propan-2-ol; H2O / 20 °C 14.1: CDI / tetrahydrofuran / 3 h / 20 °C 14.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 °C 15.1: CDI / tetrahydrofuran / 3 h / 20 °C 15.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 °C 16.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 °C 17.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 °C 17.2: 62 percent / benzene; CHCl3 / Heating 18.1: 65 percent / MgBr2*OEt2 / benzene; diethyl ether / 11 h / 0 - 20 °C | ||
Multi-step reaction with 17 steps 1.1: 61 percent / n-BuLi / tetrahydrofuran; hexane / 2 h / -78 - 20 °C 2.1: 83 percent / NaBH4 / ethanol / 20 °C 3.1: 52 percent / acetic acid / 2 h / 80 °C 4.1: 82 percent / LiAlH4 / diethyl ether / 24 h / Heating 5.1: 100 percent / DMAP / pyridine / 16 h / 20 °C 6.1: 66 percent / PPL / dimethylsulfoxide; aq. phosphate buffer / 2.5 h / 20 °C / pH 7.8 7.1: 100 percent / imidazole / dimethylformamide / 7 h / 20 °C 8.1: 100 percent / K2CO3 / methanol / 1.5 h / 20 °C 9.1: 100 percent / oxalyl chloride; DMSO; Et3N / CH2Cl2 / -78 - -40 °C 10.1: 90 percent / NaOMe / methanol / 20 °C 11.1: 93 percent / i-Pr2NEt / CH2Cl2 / 0 - 20 °C 12.1: 95 percent / 2-methyl-2-butene; NaClO2; NaH2PO4 / 2-methyl-propan-2-ol; H2O / 20 °C 13.1: CDI / tetrahydrofuran / 3 h / 20 °C 13.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 °C 14.1: CDI / tetrahydrofuran / 3 h / 20 °C 14.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 °C 15.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 °C 16.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 °C 16.2: 62 percent / benzene; CHCl3 / Heating 17.1: 65 percent / MgBr2*OEt2 / benzene; diethyl ether / 11 h / 0 - 20 °C | ||
Multi-step reaction with 17 steps 1.1: 61 percent / n-BuLi / tetrahydrofuran; hexane / 2 h / -78 - 20 °C 2.1: 83 percent / NaBH4 / ethanol / 20 °C 3.1: 29 percent / acetic acid / 2 h / 80 °C 4.1: 82 percent / LiAlH4 / diethyl ether / 24 h / Heating 5.1: 100 percent / DMAP / pyridine / 16 h / 20 °C 6.1: 66 percent / PPL / dimethylsulfoxide; aq. phosphate buffer / 2.5 h / 20 °C / pH 7.8 7.1: 100 percent / imidazole / dimethylformamide / 7 h / 20 °C 8.1: 100 percent / K2CO3 / methanol / 1.5 h / 20 °C 9.1: 100 percent / oxalyl chloride; DMSO; Et3N / CH2Cl2 / -78 - -40 °C 10.1: 90 percent / NaOMe / methanol / 20 °C 11.1: 93 percent / i-Pr2NEt / CH2Cl2 / 0 - 20 °C 12.1: 95 percent / 2-methyl-2-butene; NaClO2; NaH2PO4 / 2-methyl-propan-2-ol; H2O / 20 °C 13.1: CDI / tetrahydrofuran / 3 h / 20 °C 13.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 °C 14.1: CDI / tetrahydrofuran / 3 h / 20 °C 14.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 °C 15.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 °C 16.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 °C 16.2: 62 percent / benzene; CHCl3 / Heating 17.1: 65 percent / MgBr2*OEt2 / benzene; diethyl ether / 11 h / 0 - 20 °C |
Multi-step reaction with 17 steps 1.1: 82 percent / n-BuLi / tetrahydrofuran; hexane / 3 h / 0 - 20 °C 2.1: 90 percent / acetic acid / 2 h / 80 °C 3.1: 99 percent / H2 / 10percent Pd/C / ethyl acetate / 6 h / 2482.38 Torr 4.1: 82 percent / LiAlH4 / diethyl ether / 24 h / Heating 5.1: 100 percent / DMAP / pyridine / 16 h / 20 °C 6.1: 66 percent / PPL / dimethylsulfoxide; aq. phosphate buffer / 2.5 h / 20 °C / pH 7.8 7.1: 100 percent / imidazole / dimethylformamide / 7 h / 20 °C 8.1: 100 percent / K2CO3 / methanol / 1.5 h / 20 °C 9.1: 100 percent / oxalyl chloride; DMSO; Et3N / CH2Cl2 / -78 - -40 °C 10.1: 90 percent / NaOMe / methanol / 20 °C 11.1: 93 percent / i-Pr2NEt / CH2Cl2 / 0 - 20 °C 12.1: 95 percent / 2-methyl-2-butene; NaClO2; NaH2PO4 / 2-methyl-propan-2-ol; H2O / 20 °C 13.1: CDI / tetrahydrofuran / 3 h / 20 °C 13.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 °C 14.1: CDI / tetrahydrofuran / 3 h / 20 °C 14.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 °C 15.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 °C 16.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 °C 16.2: 62 percent / benzene; CHCl3 / Heating 17.1: 65 percent / MgBr2*OEt2 / benzene; diethyl ether / 11 h / 0 - 20 °C | ||
Multi-step reaction with 16 steps 1.1: 82 percent / n-BuLi / tetrahydrofuran; hexane / 3 h / 0 - 20 °C 2.1: 52 percent / acetic acid / 2 h / 80 °C 3.1: 82 percent / LiAlH4 / diethyl ether / 24 h / Heating 4.1: 100 percent / DMAP / pyridine / 16 h / 20 °C 5.1: 66 percent / PPL / dimethylsulfoxide; aq. phosphate buffer / 2.5 h / 20 °C / pH 7.8 6.1: 100 percent / imidazole / dimethylformamide / 7 h / 20 °C 7.1: 100 percent / K2CO3 / methanol / 1.5 h / 20 °C 8.1: 100 percent / oxalyl chloride; DMSO; Et3N / CH2Cl2 / -78 - -40 °C 9.1: 90 percent / NaOMe / methanol / 20 °C 10.1: 93 percent / i-Pr2NEt / CH2Cl2 / 0 - 20 °C 11.1: 95 percent / 2-methyl-2-butene; NaClO2; NaH2PO4 / 2-methyl-propan-2-ol; H2O / 20 °C 12.1: CDI / tetrahydrofuran / 3 h / 20 °C 12.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 °C 13.1: CDI / tetrahydrofuran / 3 h / 20 °C 13.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 °C 14.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 °C 15.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 °C 15.2: 62 percent / benzene; CHCl3 / Heating 16.1: 65 percent / MgBr2*OEt2 / benzene; diethyl ether / 11 h / 0 - 20 °C | ||
Multi-step reaction with 16 steps 1.1: 82 percent / n-BuLi / tetrahydrofuran; hexane / 3 h / 0 - 20 °C 2.1: 29 percent / acetic acid / 2 h / 80 °C 3.1: 82 percent / LiAlH4 / diethyl ether / 24 h / Heating 4.1: 100 percent / DMAP / pyridine / 16 h / 20 °C 5.1: 66 percent / PPL / dimethylsulfoxide; aq. phosphate buffer / 2.5 h / 20 °C / pH 7.8 6.1: 100 percent / imidazole / dimethylformamide / 7 h / 20 °C 7.1: 100 percent / K2CO3 / methanol / 1.5 h / 20 °C 8.1: 100 percent / oxalyl chloride; DMSO; Et3N / CH2Cl2 / -78 - -40 °C 9.1: 90 percent / NaOMe / methanol / 20 °C 10.1: 93 percent / i-Pr2NEt / CH2Cl2 / 0 - 20 °C 11.1: 95 percent / 2-methyl-2-butene; NaClO2; NaH2PO4 / 2-methyl-propan-2-ol; H2O / 20 °C 12.1: CDI / tetrahydrofuran / 3 h / 20 °C 12.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 °C 13.1: CDI / tetrahydrofuran / 3 h / 20 °C 13.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 °C 14.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 °C 15.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 °C 15.2: 62 percent / benzene; CHCl3 / Heating 16.1: 65 percent / MgBr2*OEt2 / benzene; diethyl ether / 11 h / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 17 steps 1.1: 83 percent / NaBH4 / ethanol / 20 °C 2.1: 90 percent / acetic acid / 2 h / 80 °C 3.1: 99 percent / H2 / 10percent Pd/C / ethyl acetate / 6 h / 2482.38 Torr 4.1: 82 percent / LiAlH4 / diethyl ether / 24 h / Heating 5.1: 100 percent / DMAP / pyridine / 16 h / 20 °C 6.1: 66 percent / PPL / dimethylsulfoxide; aq. phosphate buffer / 2.5 h / 20 °C / pH 7.8 7.1: 100 percent / imidazole / dimethylformamide / 7 h / 20 °C 8.1: 100 percent / K2CO3 / methanol / 1.5 h / 20 °C 9.1: 100 percent / oxalyl chloride; DMSO; Et3N / CH2Cl2 / -78 - -40 °C 10.1: 90 percent / NaOMe / methanol / 20 °C 11.1: 93 percent / i-Pr2NEt / CH2Cl2 / 0 - 20 °C 12.1: 95 percent / 2-methyl-2-butene; NaClO2; NaH2PO4 / 2-methyl-propan-2-ol; H2O / 20 °C 13.1: CDI / tetrahydrofuran / 3 h / 20 °C 13.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 °C 14.1: CDI / tetrahydrofuran / 3 h / 20 °C 14.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 °C 15.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 °C 16.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 °C 16.2: 62 percent / benzene; CHCl3 / Heating 17.1: 65 percent / MgBr2*OEt2 / benzene; diethyl ether / 11 h / 0 - 20 °C | ||
Multi-step reaction with 16 steps 1.1: 83 percent / NaBH4 / ethanol / 20 °C 2.1: 52 percent / acetic acid / 2 h / 80 °C 3.1: 82 percent / LiAlH4 / diethyl ether / 24 h / Heating 4.1: 100 percent / DMAP / pyridine / 16 h / 20 °C 5.1: 66 percent / PPL / dimethylsulfoxide; aq. phosphate buffer / 2.5 h / 20 °C / pH 7.8 6.1: 100 percent / imidazole / dimethylformamide / 7 h / 20 °C 7.1: 100 percent / K2CO3 / methanol / 1.5 h / 20 °C 8.1: 100 percent / oxalyl chloride; DMSO; Et3N / CH2Cl2 / -78 - -40 °C 9.1: 90 percent / NaOMe / methanol / 20 °C 10.1: 93 percent / i-Pr2NEt / CH2Cl2 / 0 - 20 °C 11.1: 95 percent / 2-methyl-2-butene; NaClO2; NaH2PO4 / 2-methyl-propan-2-ol; H2O / 20 °C 12.1: CDI / tetrahydrofuran / 3 h / 20 °C 12.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 °C 13.1: CDI / tetrahydrofuran / 3 h / 20 °C 13.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 °C 14.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 °C 15.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 °C 15.2: 62 percent / benzene; CHCl3 / Heating 16.1: 65 percent / MgBr2*OEt2 / benzene; diethyl ether / 11 h / 0 - 20 °C | ||
Multi-step reaction with 16 steps 1.1: 83 percent / NaBH4 / ethanol / 20 °C 2.1: 29 percent / acetic acid / 2 h / 80 °C 3.1: 82 percent / LiAlH4 / diethyl ether / 24 h / Heating 4.1: 100 percent / DMAP / pyridine / 16 h / 20 °C 5.1: 66 percent / PPL / dimethylsulfoxide; aq. phosphate buffer / 2.5 h / 20 °C / pH 7.8 6.1: 100 percent / imidazole / dimethylformamide / 7 h / 20 °C 7.1: 100 percent / K2CO3 / methanol / 1.5 h / 20 °C 8.1: 100 percent / oxalyl chloride; DMSO; Et3N / CH2Cl2 / -78 - -40 °C 9.1: 90 percent / NaOMe / methanol / 20 °C 10.1: 93 percent / i-Pr2NEt / CH2Cl2 / 0 - 20 °C 11.1: 95 percent / 2-methyl-2-butene; NaClO2; NaH2PO4 / 2-methyl-propan-2-ol; H2O / 20 °C 12.1: CDI / tetrahydrofuran / 3 h / 20 °C 12.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 °C 13.1: CDI / tetrahydrofuran / 3 h / 20 °C 13.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 °C 14.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 °C 15.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 °C 15.2: 62 percent / benzene; CHCl3 / Heating 16.1: 65 percent / MgBr2*OEt2 / benzene; diethyl ether / 11 h / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 16 steps 1.1: 90 percent / acetic acid / 2 h / 80 °C 2.1: 99 percent / H2 / 10percent Pd/C / ethyl acetate / 6 h / 2482.38 Torr 3.1: 82 percent / LiAlH4 / diethyl ether / 24 h / Heating 4.1: 100 percent / DMAP / pyridine / 16 h / 20 °C 5.1: 66 percent / PPL / dimethylsulfoxide; aq. phosphate buffer / 2.5 h / 20 °C / pH 7.8 6.1: 100 percent / imidazole / dimethylformamide / 7 h / 20 °C 7.1: 100 percent / K2CO3 / methanol / 1.5 h / 20 °C 8.1: 100 percent / oxalyl chloride; DMSO; Et3N / CH2Cl2 / -78 - -40 °C 9.1: 90 percent / NaOMe / methanol / 20 °C 10.1: 93 percent / i-Pr2NEt / CH2Cl2 / 0 - 20 °C 11.1: 95 percent / 2-methyl-2-butene; NaClO2; NaH2PO4 / 2-methyl-propan-2-ol; H2O / 20 °C 12.1: CDI / tetrahydrofuran / 3 h / 20 °C 12.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 °C 13.1: CDI / tetrahydrofuran / 3 h / 20 °C 13.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 °C 14.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 °C 15.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 °C 15.2: 62 percent / benzene; CHCl3 / Heating 16.1: 65 percent / MgBr2*OEt2 / benzene; diethyl ether / 11 h / 0 - 20 °C | ||
Multi-step reaction with 15 steps 1.1: 52 percent / acetic acid / 2 h / 80 °C 2.1: 82 percent / LiAlH4 / diethyl ether / 24 h / Heating 3.1: 100 percent / DMAP / pyridine / 16 h / 20 °C 4.1: 66 percent / PPL / dimethylsulfoxide; aq. phosphate buffer / 2.5 h / 20 °C / pH 7.8 5.1: 100 percent / imidazole / dimethylformamide / 7 h / 20 °C 6.1: 100 percent / K2CO3 / methanol / 1.5 h / 20 °C 7.1: 100 percent / oxalyl chloride; DMSO; Et3N / CH2Cl2 / -78 - -40 °C 8.1: 90 percent / NaOMe / methanol / 20 °C 9.1: 93 percent / i-Pr2NEt / CH2Cl2 / 0 - 20 °C 10.1: 95 percent / 2-methyl-2-butene; NaClO2; NaH2PO4 / 2-methyl-propan-2-ol; H2O / 20 °C 11.1: CDI / tetrahydrofuran / 3 h / 20 °C 11.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 °C 12.1: CDI / tetrahydrofuran / 3 h / 20 °C 12.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 °C 13.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 °C 14.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 °C 14.2: 62 percent / benzene; CHCl3 / Heating 15.1: 65 percent / MgBr2*OEt2 / benzene; diethyl ether / 11 h / 0 - 20 °C | ||
Multi-step reaction with 15 steps 1.1: 29 percent / acetic acid / 2 h / 80 °C 2.1: 82 percent / LiAlH4 / diethyl ether / 24 h / Heating 3.1: 100 percent / DMAP / pyridine / 16 h / 20 °C 4.1: 66 percent / PPL / dimethylsulfoxide; aq. phosphate buffer / 2.5 h / 20 °C / pH 7.8 5.1: 100 percent / imidazole / dimethylformamide / 7 h / 20 °C 6.1: 100 percent / K2CO3 / methanol / 1.5 h / 20 °C 7.1: 100 percent / oxalyl chloride; DMSO; Et3N / CH2Cl2 / -78 - -40 °C 8.1: 90 percent / NaOMe / methanol / 20 °C 9.1: 93 percent / i-Pr2NEt / CH2Cl2 / 0 - 20 °C 10.1: 95 percent / 2-methyl-2-butene; NaClO2; NaH2PO4 / 2-methyl-propan-2-ol; H2O / 20 °C 11.1: CDI / tetrahydrofuran / 3 h / 20 °C 11.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 °C 12.1: CDI / tetrahydrofuran / 3 h / 20 °C 12.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 °C 13.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 °C 14.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 °C 14.2: 62 percent / benzene; CHCl3 / Heating 15.1: 65 percent / MgBr2*OEt2 / benzene; diethyl ether / 11 h / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 13 steps 1.1: 100 percent / DMAP / pyridine / 16 h / 20 °C 2.1: 66 percent / PPL / dimethylsulfoxide; aq. phosphate buffer / 2.5 h / 20 °C / pH 7.8 3.1: 100 percent / imidazole / dimethylformamide / 7 h / 20 °C 4.1: 100 percent / K2CO3 / methanol / 1.5 h / 20 °C 5.1: 100 percent / oxalyl chloride; DMSO; Et3N / CH2Cl2 / -78 - -40 °C 6.1: 90 percent / NaOMe / methanol / 20 °C 7.1: 93 percent / i-Pr2NEt / CH2Cl2 / 0 - 20 °C 8.1: 95 percent / 2-methyl-2-butene; NaClO2; NaH2PO4 / 2-methyl-propan-2-ol; H2O / 20 °C 9.1: CDI / tetrahydrofuran / 3 h / 20 °C 9.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 °C 10.1: CDI / tetrahydrofuran / 3 h / 20 °C 10.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 °C 11.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 °C 12.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 °C 12.2: 62 percent / benzene; CHCl3 / Heating 13.1: 65 percent / MgBr2*OEt2 / benzene; diethyl ether / 11 h / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 14 steps 1.1: 82 percent / LiAlH4 / diethyl ether / 24 h / Heating 2.1: 100 percent / DMAP / pyridine / 16 h / 20 °C 3.1: 66 percent / PPL / dimethylsulfoxide; aq. phosphate buffer / 2.5 h / 20 °C / pH 7.8 4.1: 100 percent / imidazole / dimethylformamide / 7 h / 20 °C 5.1: 100 percent / K2CO3 / methanol / 1.5 h / 20 °C 6.1: 100 percent / oxalyl chloride; DMSO; Et3N / CH2Cl2 / -78 - -40 °C 7.1: 90 percent / NaOMe / methanol / 20 °C 8.1: 93 percent / i-Pr2NEt / CH2Cl2 / 0 - 20 °C 9.1: 95 percent / 2-methyl-2-butene; NaClO2; NaH2PO4 / 2-methyl-propan-2-ol; H2O / 20 °C 10.1: CDI / tetrahydrofuran / 3 h / 20 °C 10.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 °C 11.1: CDI / tetrahydrofuran / 3 h / 20 °C 11.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 °C 12.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 °C 13.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 °C 13.2: 62 percent / benzene; CHCl3 / Heating 14.1: 65 percent / MgBr2*OEt2 / benzene; diethyl ether / 11 h / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 15 steps 1.1: 99 percent / H2 / 10percent Pd/C / ethyl acetate / 6 h / 2482.38 Torr 2.1: 82 percent / LiAlH4 / diethyl ether / 24 h / Heating 3.1: 100 percent / DMAP / pyridine / 16 h / 20 °C 4.1: 66 percent / PPL / dimethylsulfoxide; aq. phosphate buffer / 2.5 h / 20 °C / pH 7.8 5.1: 100 percent / imidazole / dimethylformamide / 7 h / 20 °C 6.1: 100 percent / K2CO3 / methanol / 1.5 h / 20 °C 7.1: 100 percent / oxalyl chloride; DMSO; Et3N / CH2Cl2 / -78 - -40 °C 8.1: 90 percent / NaOMe / methanol / 20 °C 9.1: 93 percent / i-Pr2NEt / CH2Cl2 / 0 - 20 °C 10.1: 95 percent / 2-methyl-2-butene; NaClO2; NaH2PO4 / 2-methyl-propan-2-ol; H2O / 20 °C 11.1: CDI / tetrahydrofuran / 3 h / 20 °C 11.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 °C 12.1: CDI / tetrahydrofuran / 3 h / 20 °C 12.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 °C 13.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 °C 14.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 °C 14.2: 62 percent / benzene; CHCl3 / Heating 15.1: 65 percent / MgBr2*OEt2 / benzene; diethyl ether / 11 h / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 12 steps 1.1: 66 percent / PPL / dimethylsulfoxide; aq. phosphate buffer / 2.5 h / 20 °C / pH 7.8 2.1: 100 percent / imidazole / dimethylformamide / 7 h / 20 °C 3.1: 100 percent / K2CO3 / methanol / 1.5 h / 20 °C 4.1: 100 percent / oxalyl chloride; DMSO; Et3N / CH2Cl2 / -78 - -40 °C 5.1: 90 percent / NaOMe / methanol / 20 °C 6.1: 93 percent / i-Pr2NEt / CH2Cl2 / 0 - 20 °C 7.1: 95 percent / 2-methyl-2-butene; NaClO2; NaH2PO4 / 2-methyl-propan-2-ol; H2O / 20 °C 8.1: CDI / tetrahydrofuran / 3 h / 20 °C 8.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 °C 9.1: CDI / tetrahydrofuran / 3 h / 20 °C 9.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 °C 10.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 °C 11.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 °C 11.2: 62 percent / benzene; CHCl3 / Heating 12.1: 65 percent / MgBr2*OEt2 / benzene; diethyl ether / 11 h / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 11 steps 1.1: 100 percent / imidazole / dimethylformamide / 7 h / 20 °C 2.1: 100 percent / K2CO3 / methanol / 1.5 h / 20 °C 3.1: 100 percent / oxalyl chloride; DMSO; Et3N / CH2Cl2 / -78 - -40 °C 4.1: 90 percent / NaOMe / methanol / 20 °C 5.1: 93 percent / i-Pr2NEt / CH2Cl2 / 0 - 20 °C 6.1: 95 percent / 2-methyl-2-butene; NaClO2; NaH2PO4 / 2-methyl-propan-2-ol; H2O / 20 °C 7.1: CDI / tetrahydrofuran / 3 h / 20 °C 7.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 °C 8.1: CDI / tetrahydrofuran / 3 h / 20 °C 8.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 °C 9.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 °C 10.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 °C 10.2: 62 percent / benzene; CHCl3 / Heating 11.1: 65 percent / MgBr2*OEt2 / benzene; diethyl ether / 11 h / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1.1: 93 percent / i-Pr2NEt / CH2Cl2 / 0 - 20 °C 2.1: 95 percent / 2-methyl-2-butene; NaClO2; NaH2PO4 / 2-methyl-propan-2-ol; H2O / 20 °C 3.1: CDI / tetrahydrofuran / 3 h / 20 °C 3.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 °C 4.1: CDI / tetrahydrofuran / 3 h / 20 °C 4.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 °C 5.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 °C 6.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 °C 6.2: 62 percent / benzene; CHCl3 / Heating 7.1: 65 percent / MgBr2*OEt2 / benzene; diethyl ether / 11 h / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1.1: 90 percent / NaOMe / methanol / 20 °C 2.1: 93 percent / i-Pr2NEt / CH2Cl2 / 0 - 20 °C 3.1: 95 percent / 2-methyl-2-butene; NaClO2; NaH2PO4 / 2-methyl-propan-2-ol; H2O / 20 °C 4.1: CDI / tetrahydrofuran / 3 h / 20 °C 4.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 °C 5.1: CDI / tetrahydrofuran / 3 h / 20 °C 5.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 °C 6.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 °C 7.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 °C 7.2: 62 percent / benzene; CHCl3 / Heating 8.1: 65 percent / MgBr2*OEt2 / benzene; diethyl ether / 11 h / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1.1: 100 percent / oxalyl chloride; DMSO; Et3N / CH2Cl2 / -78 - -40 °C 2.1: 90 percent / NaOMe / methanol / 20 °C 3.1: 93 percent / i-Pr2NEt / CH2Cl2 / 0 - 20 °C 4.1: 95 percent / 2-methyl-2-butene; NaClO2; NaH2PO4 / 2-methyl-propan-2-ol; H2O / 20 °C 5.1: CDI / tetrahydrofuran / 3 h / 20 °C 5.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 °C 6.1: CDI / tetrahydrofuran / 3 h / 20 °C 6.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 °C 7.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 °C 8.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 °C 8.2: 62 percent / benzene; CHCl3 / Heating 9.1: 65 percent / MgBr2*OEt2 / benzene; diethyl ether / 11 h / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 10 steps 1.1: 100 percent / K2CO3 / methanol / 1.5 h / 20 °C 2.1: 100 percent / oxalyl chloride; DMSO; Et3N / CH2Cl2 / -78 - -40 °C 3.1: 90 percent / NaOMe / methanol / 20 °C 4.1: 93 percent / i-Pr2NEt / CH2Cl2 / 0 - 20 °C 5.1: 95 percent / 2-methyl-2-butene; NaClO2; NaH2PO4 / 2-methyl-propan-2-ol; H2O / 20 °C 6.1: CDI / tetrahydrofuran / 3 h / 20 °C 6.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 °C 7.1: CDI / tetrahydrofuran / 3 h / 20 °C 7.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 °C 8.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 °C 9.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 °C 9.2: 62 percent / benzene; CHCl3 / Heating 10.1: 65 percent / MgBr2*OEt2 / benzene; diethyl ether / 11 h / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1.1: 95 percent / 2-methyl-2-butene; NaClO2; NaH2PO4 / 2-methyl-propan-2-ol; H2O / 20 °C 2.1: CDI / tetrahydrofuran / 3 h / 20 °C 2.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 °C 3.1: CDI / tetrahydrofuran / 3 h / 20 °C 3.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 °C 4.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 °C 5.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 °C 5.2: 62 percent / benzene; CHCl3 / Heating 6.1: 65 percent / MgBr2*OEt2 / benzene; diethyl ether / 11 h / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: CDI / tetrahydrofuran / 3 h / 20 °C 1.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 °C 2.1: CDI / tetrahydrofuran / 3 h / 20 °C 2.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 °C 3.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 °C 4.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 °C 4.2: 62 percent / benzene; CHCl3 / Heating 5.1: 65 percent / MgBr2*OEt2 / benzene; diethyl ether / 11 h / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 °C 2.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 °C 2.2: 62 percent / benzene; CHCl3 / Heating 3.1: 65 percent / MgBr2*OEt2 / benzene; diethyl ether / 11 h / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: CDI / tetrahydrofuran / 3 h / 20 °C 1.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 °C 2.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 °C 3.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 °C 3.2: 62 percent / benzene; CHCl3 / Heating 4.1: 65 percent / MgBr2*OEt2 / benzene; diethyl ether / 11 h / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 °C 1.2: 62 percent / benzene; CHCl3 / Heating 2.1: 65 percent / MgBr2*OEt2 / benzene; diethyl ether / 11 h / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 200 mg / PDC / CH2Cl2 / 3 h / Ambient temperature 2: 1 percent KOH / methanol | ||
Multi-step reaction with 2 steps 1: CrO3 / pyridine / 3 h / Ambient temperature 2: t-BuOK, H2O / 2-methyl-propan-2-ol / 0.17 h / Ambient temperature | ||
Multi-step reaction with 2 steps 1: CrO3 / pyridine / 3 h / Ambient temperature 2: 10percent KOH / methanol / 30 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: NaN3, TFA / CHCl3 / 1 h 2: 63 percent / H2 / 5percent Pd/C / ethanol / 4 h / 40 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: SOCl2 / CHCl3 / 0.17 h / Ambient temperature 2: NaN3 / dimethylformamide / Ambient temperature 3: 61 percent / H2 / 5percent Pd/C / ethanol / 4 h / 40 °C | ||
Multi-step reaction with 2 steps 1: NaN3, TFA / CHCl3 / 1 h 2: 61 percent / H2 / 5percent Pd/C / ethanol / 4 h / 40 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: SOCl2 / CHCl3 / 0.17 h / Ambient temperature 2: NaN3 / dimethylformamide / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: NaN3, TFA / CHCl3 / 1 h 2: 63 percent / H2 / 5percent Pd/C / ethanol / 4 h / 40 °C 3: 88 percent / pyridine / 1 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: SOCl2 / CHCl3 / 0.17 h / Ambient temperature 2: NaN3 / dimethylformamide / Ambient temperature 3: 61 percent / H2 / 5percent Pd/C / ethanol / 4 h / 40 °C 4: 88 percent / pyridine / 1 h / 0 °C | ||
Multi-step reaction with 3 steps 1: NaN3, TFA / CHCl3 / 1 h 2: 61 percent / H2 / 5percent Pd/C / ethanol / 4 h / 40 °C 3: 88 percent / pyridine / 1 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 74 percent / xylene / 36 h / 210 °C 2: 94 percent / lithium tri-tert-butoxyaluminum hydride / tetrahydrofuran / 3.5 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1: 100 percent / N-bromosuccinimide, DMSO / tetrahydrofuran / 6 h / 0 °C 2: 79 percent / azobis(isobutyronitrile), tri-n-butyltin hydride / toluene / 4 h / 120 °C 3: 87 percent / pyridinium dichromate, 3A molecular sieves / CH2Cl2 / 4 h / Ambient temperature 4: 1.) 5 N sodium hydroxide, 2.) p-toluenesulfonic acid / 1.) THF, H2O, 26 h, r. t., 2.) aq. EtOH, 60 - 65 deg C, 24 h 5: 74 percent / xylene / 36 h / 210 °C 6: 94 percent / lithium tri-tert-butoxyaluminum hydride / tetrahydrofuran / 3.5 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 1.) 5 N sodium hydroxide, 2.) p-toluenesulfonic acid / 1.) THF, H2O, 26 h, r. t., 2.) aq. EtOH, 60 - 65 deg C, 24 h 2: 74 percent / xylene / 36 h / 210 °C 3: 94 percent / lithium tri-tert-butoxyaluminum hydride / tetrahydrofuran / 3.5 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 87 percent / pyridinium dichromate, 3A molecular sieves / CH2Cl2 / 4 h / Ambient temperature 2: 1.) 5 N sodium hydroxide, 2.) p-toluenesulfonic acid / 1.) THF, H2O, 26 h, r. t., 2.) aq. EtOH, 60 - 65 deg C, 24 h 3: 74 percent / xylene / 36 h / 210 °C 4: 94 percent / lithium tri-tert-butoxyaluminum hydride / tetrahydrofuran / 3.5 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: 79 percent / azobis(isobutyronitrile), tri-n-butyltin hydride / toluene / 4 h / 120 °C 2: 87 percent / pyridinium dichromate, 3A molecular sieves / CH2Cl2 / 4 h / Ambient temperature 3: 1.) 5 N sodium hydroxide, 2.) p-toluenesulfonic acid / 1.) THF, H2O, 26 h, r. t., 2.) aq. EtOH, 60 - 65 deg C, 24 h 4: 74 percent / xylene / 36 h / 210 °C 5: 94 percent / lithium tri-tert-butoxyaluminum hydride / tetrahydrofuran / 3.5 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1: 96 percent / 5 N aq. sodium hydroxide / methanol; H2O / 8 h / 60 °C 2: 2.) 4-(dimethylamino)pyridine, trimethylamine / 1.) ether, THF, 10 min, 2.) CH2Cl2, 0 deg C, 30 min, 3.) CH2Cl2, 10 min, r. t. 3: 100 percent / N-bromosuccinimide, DMSO / tetrahydrofuran / 6 h / 0 °C 4: 79 percent / azobis(isobutyronitrile), tri-n-butyltin hydride / toluene / 4 h / 120 °C 5: 87 percent / pyridinium dichromate, 3A molecular sieves / CH2Cl2 / 4 h / Ambient temperature 6: 1.) 5 N sodium hydroxide, 2.) p-toluenesulfonic acid / 1.) THF, H2O, 26 h, r. t., 2.) aq. EtOH, 60 - 65 deg C, 24 h 7: 74 percent / xylene / 36 h / 210 °C 8: 94 percent / lithium tri-tert-butoxyaluminum hydride / tetrahydrofuran / 3.5 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1: 2.) 4-(dimethylamino)pyridine, trimethylamine / 1.) ether, THF, 10 min, 2.) CH2Cl2, 0 deg C, 30 min, 3.) CH2Cl2, 10 min, r. t. 2: 100 percent / N-bromosuccinimide, DMSO / tetrahydrofuran / 6 h / 0 °C 3: 79 percent / azobis(isobutyronitrile), tri-n-butyltin hydride / toluene / 4 h / 120 °C 4: 87 percent / pyridinium dichromate, 3A molecular sieves / CH2Cl2 / 4 h / Ambient temperature 5: 1.) 5 N sodium hydroxide, 2.) p-toluenesulfonic acid / 1.) THF, H2O, 26 h, r. t., 2.) aq. EtOH, 60 - 65 deg C, 24 h 6: 74 percent / xylene / 36 h / 210 °C 7: 94 percent / lithium tri-tert-butoxyaluminum hydride / tetrahydrofuran / 3.5 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 93 percent / 2,6-lutidine / CH2Cl2 / 4 h / 0 °C 2: 1.) lithium hexamethyldisilazide, 2.) acetic acid / 1.) THF, 0 deg C, 40 min, 2.) THF, -78 deg C, 10 min |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 93 percent / 2,6-lutidine / CH2Cl2 / 4 h / 0 °C 2: 1.) lithium hexamethyldisilazide, 2.) acetic acid / 1.) THF, 0 deg C, 40 min, 2.) THF, -78 deg C, 10 min 3: 79 percent / triethylammonium fluoride / acetonitrile / 72 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: CrO3 / pyridine / 3 h / Ambient temperature 2: t-BuOK, H2O / 2-methyl-propan-2-ol / 0.17 h / Ambient temperature 3: HCl / CH2Cl2 | ||
Multi-step reaction with 4 steps 1: CrO3 / pyridine / 3 h / Ambient temperature 2: 10percent KOH / methanol / 30 h / Ambient temperature 3: HCl / CH2Cl2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: CrO3 / pyridine / 3 h / Ambient temperature 2: t-BuOK, H2O / 2-methyl-propan-2-ol / 0.17 h / Ambient temperature 3: HCl / CH2Cl2 | ||
Multi-step reaction with 3 steps 1: CrO3 / pyridine / 3 h / Ambient temperature 2: 10percent KOH / methanol / 30 h / Ambient temperature 3: HCl / CH2Cl2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: CrO3 / pyridine / 3 h / Ambient temperature 2: 10percent KOH / methanol / 30 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: CrO3 / pyridine / 3 h / Ambient temperature 2: 10percent KOH / methanol / 30 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: ethanol; sodium acetate 2: acetone; aqueous hydrochloric acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: pyridine 2: 240 °C | ||
With acetic anhydride at 100℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: pyridine 2: 240 °C 3: Raney nickel; ethanol / 60 °C / 73550.8 Torr / Hydrogenation |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; diisopropyl-carbodiimide In dichloromethane at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: sodium carbonate / trans-di(μ-acetato)-bis[o-(di-o-tolylphosphino)benzyl]-dipalladium(II) / ethanol / 15 h / Reflux 2.1: osmium(VIII) oxide; 4-methylmorpholine N-oxide / dichloromethane; water / 4 h / 20 °C 2.2: 1 h / 20 °C 3.1: sodium tetrahydroborate; methanol / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: chromium(VI) oxide; pyridine / dichloromethane / 3 h / 20 °C 2.1: pyridine; hydroxylamine hydrochloride / ethanol / 72 h / Reflux 3.1: sodium hydride / tetrahydrofuran / 0.5 h / -10 °C 3.2: 3 h / -10 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: chromium(VI) oxide; pyridine / dichloromethane / 3 h / 20 °C 2.1: pyridine; hydroxylamine hydrochloride / ethanol / 72 h / Reflux 3.1: sodium hydride / tetrahydrofuran / 0.5 h / -10 °C 3.2: 3 h / -10 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: chromium(VI) oxide; pyridine / dichloromethane / 3 h / 20 °C 2.1: pyridine; hydroxylamine hydrochloride / ethanol / 72 h / Reflux 3.1: sodium hydride / tetrahydrofuran / 0.5 h / -10 °C 3.2: 48 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: chromium(VI) oxide; pyridine / dichloromethane / 3 h / 20 °C 2: pyridine; hydroxylamine hydrochloride / ethanol / 72 h / Reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: chromium(VI) oxide; pyridine / dichloromethane / 3 h / 20 °C 2.1: pyridine; hydroxylamine hydrochloride / ethanol / 72 h / Reflux 3.1: sodium hydride / tetrahydrofuran / 0.5 h / -10 °C 3.2: 3 h / -10 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: chromium(VI) oxide; pyridine / dichloromethane / 3 h / 20 °C 2.1: pyridine; hydroxylamine hydrochloride / ethanol / 72 h / Reflux 3.1: sodium hydride / tetrahydrofuran / 0.5 h / -10 °C 3.2: 3 h / -10 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: chromium(VI) oxide; pyridine / dichloromethane / 3 h / 20 °C 2.1: pyridine; hydroxylamine hydrochloride / ethanol / 72 h / Reflux 3.1: sodium hydride / tetrahydrofuran / 0.5 h / -10 °C 3.2: 3 h / -10 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: chromium(VI) oxide; pyridine / dichloromethane / 3 h / 20 °C 2.1: pyridine; hydroxylamine hydrochloride / ethanol / 72 h / Reflux 3.1: sodium hydride / tetrahydrofuran / 0.5 h / -10 °C 3.2: 3 h / -10 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: picropodophyllotoxin With boron trichloride In hexane at -70℃; Stage #2: With water; barium carbonate In acetone for 1h; Reflux; | 3 Example 3 (3aR.4R,9R.9aS)-4.6.7-trihvdroxy-9-(3,4,5-trimethoxyphenyl)-3a,4.9.9a- tetrahvdronaphthor2,3-c1furan-1(3H)-one HO A solution of boron trichloride (BCI3, 1 ml.) 1 M in hexanes was cooled to ca -70 °C in a dry vial and PPP (100 mg, 0.24 mmol) was added over 40 minutes as a suspension in dry dichloromethane (3 ml_). The off white suspension was stirred at the same temperature for 2 hours and then transferred to Dewar with dry ice over night. The mixture was poured over ice-water (4.2 mL) and extracted once with ethyl acetate. The organic layer was washed with brine until pH 6-7, dried over Na2S04, filtered and evaporated. The solid material was suspended in water: acetone: barium carbonate (1mL: 1ml_: 67 mg) and refluxed for an hour. The precipitate was filtered off and the pH of the filtrate was adjusted to 2-3 by 1 M hydrochloric acid and extracted five times with ethyl acetate. The combined organic layers were washed with brine until the pH was 6 again, dried over Na2S04 and evaporated to afford 16 mg of the crude product. The crude product was used as such. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 4.5h; | 3 Example 3 (5R,5aR,8aS,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5.5a,6,8,8a.9- hexahvdrofuror3',4':6.71naphthor2,3-diri,31dioxol-5-yl pentanoate Example 3 (5R,5aR,8aS,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5.5a,6,8,8a.9- hexahvdrofuror3',4':6.71naphthor2,3-diri,31dioxol-5-yl pentanoate PPP (41 mg, 0.10 mmol), DMAP (6 mg, 0.05 mmol) and valeric acid (12 mg, 0.12 mmol) were weighed in a vial. Dry dichloromethane (1.5 mL) was added followed by EDC-HCI (25 mg, 0.13 mmol) at room temperature. The reaction mixture was stirred for 4.5 hours. Then more dichloromethane was added and the solution was washed with 0.1 M HCI, saturated NaHC03 and brine. The organic layer was dried and evaporated to give the product in 43 mg yield and 87% purity LCMS (ACE 3 C8, 50 x 3.0 mm, 10% to 97% acetonitrile in 3 min in 0.1% TFA in water, 1 mL/min), MS ESI+ m/z 397, rt 2.506. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 72h; | 4 Example 4 (5R,5aR,8aS,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5,5a,6,8,8a,9- hexahydrofuror3'.4':6.7rlnaphthor2,3-diri.31dioxol-5-yl heptanoate Example 4 (5R,5aR,8aS,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5,5a,6,8,8a,9- hexahydrofuror3'.4':6.7rlnaphthor2,3-diri.31dioxol-5-yl heptanoate PPP (41 mg, 0.10 mmol), DMAP (6 mg, 0.05 mmol) and heptanoic acid (16 mg, 0.12 mmol) were weighed in a vial. Dry dichloromethane (1.5 ml_) was added followed by EDC- HCI (25 mg, 0.13 mmol) at room temperature. The reaction mixture was stirred for three days. Then more dichloromethane was added and the solution was washed with 0.1 M HCI, saturated NaHC03 and brine. The crude product (54 mg) was purified by flash chromatography using 0-4% methanol in dichloromethane to give the product in 42 mg yield and 91% purity LCMS (ACE 3 C8, 50 x 3.0 mm, 10% to 97% acetonitrile in 3 min in 0.1% TFA in water, 1 mUmin), MS ESI+ m/z 397, rt 2.687. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 72h; | Example 5 (5R.5aR.8aS,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5,5a,6,8,8a,9- hexahvdrofuror3',4':6,71naphthor2,3-diri,31dioxol-5-yl undecanoate PPP (41 mg, 0.1 mmol), DMAP (6 mg, 0.05 mmol) and the undecanoic (23 mg, 0.09 mmol) acid were weighed in a vial. Dry dichloromethane (1.5 mL) was added and EDC- HCI (23 mg, 0.12 mmol) was added at room temperature. The reaction mixture was stirred for three days. More dichloromethane was added and the solution was washed with 0.1 M HCI (aq), saturated NaHC03 and brine. The crude product (55 mg) was purified by flash chromatography using 2-4% methanol in dichloromethane to give the title compound in 77% yield (45 mg) and 96% purity according to LCMS (ACE 3 C8, 50 x 3.0 mm, 10% to 97% acetonitrile in 3 min in 0.1% TFA in water, 1 mL/min), MS ESI+ m/z 397, rt 3.107. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38 mg | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; | 6 Example 6 (5R.5aR,8aS,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5.5a,6,8,8a,9- hexahvdrofuror3'.4':6.71naphthor2,3-din.31dioxol-5-vi palmitate Example 6 (5R.5aR,8aS,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5.5a,6,8,8a,9- hexahvdrofuror3'.4':6.71naphthor2,3-din.31dioxol-5-vi palmitate PPP (41 mg, 0.10 mmol), DMAP (6 mg, 0.05 mmol) and palmitic acid (23 mg, 0.09 mmol) were weighed in a vial. Dry dichloromethane was added followed by EDC-HCI (23 mg, 0.12 mmol) at room temperature. The reaction mixture was stirred overnight. More dichloromethane was added and the solution was washed with 0.1 M HCI, saturated NaHC03 and brine. The crude product (54 mg) was purified by flash chromatography (1.5 x 5 cm) using 1% methanol in dichloromethane to give the title product in 38 mg yield and 100% purity according to LCMS (ACE 3 C8, 50 x 3.0 mm, 10% to 97% acetonitrile in 3 min in 0.1% TFA in water, 1 mL/min), MS ESI+ m/z 397, rt 2.104. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 96h; | 7 Example 7 3-oxo-3-(((5R,5aR.8aS,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5.5a,6,8,8a,9- hexahvdrofuror3',4':6,71naphthor2,3-diri.31dioxol-5-yl)oxy)propanoic acid Example 7 3-oxo-3-(((5R,5aR.8aS,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5.5a,6,8,8a,9- hexahvdrofuror3',4':6,71naphthor2,3-diri.31dioxol-5-yl)oxy)propanoic acid PPP (41 mg, 0.10 mmol), DMAP (6 mg, 0.05 mmol) and malonic acid (11 mg, 0.1 mmol) were weighed in a vial. Dry dichloromethane (1.5 ml.) was added followed by EDC-HCI (19 mg, 0.1 mmol) at room temperature. The reaction mixture was stirred for 4 days. Then more dichloromethane was added and the solution was washed with 0.1 M HCI, saturated NaHC03 and brine. The crude product (39 mg) was purified by flash chromatography using 2% methanol in dichloromethane as eluent to give the product in 15 mg yield and 94% purity LCMS (ACE 3 C8, 50 x 3.0 mm, 10% to 97% acetonitrile in 3 min in 0.1% TFA in water, 1 mL/min), MS ESI+ m/z 397, rt 2.082. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; | 8 Example 8 9-oxo-9-f((5R,5aR,8aS,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5,5a,6,8,8a,9- hexahvdrofuror3'.4':6,71naphthor2,3-diri,31dioxol-5-yl)oxy)nonanoic acid Example 8 9-oxo-9-f((5R,5aR,8aS,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5,5a,6,8,8a,9- hexahvdrofuror3'.4':6,71naphthor2,3-diri,31dioxol-5-yl)oxy)nonanoic acid PPP (41 mg, 0.10 mmol), DMAP (6 mg, 0.05 mmol) and azelaic acid (17 mg, 0.09 mmol) were weighed in a vial. Dry dichloromethane was added followed by EDC-HCI (17 mg, 0.09 mmol) at room temperature. The reaction mixture was stirred overnight. More dichloromethane was added and the solution was washed with 0.1 M HCI, saturated NaHC03 and brine. The crude product (49 mg) was purified by flash chromatography using methanol : dichloromethane 1 : 40 and 1 : 20 to give the product in 20 mg yield and 90% purity according to LCMS (ACE 3 C8, 50 x 3.0 mm, 10% to 97% acetonitrile in 3 min in 0.1% TFA in water, 1 mL/min), MS ESI+ m/z 397, rt 1.585 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 72h; | 19 Example 19 bis((5R.5aR.8aS,9R)-8-oxo-9-(3A5-trimethoxyphenyl)-5,5a,6,8,8a.9- hexahvdrofuror3'.4':6,71naphthor2,3-cnri.31dioxol-5-yl) nonanedioate Example 19 bis((5R.5aR.8aS,9R)-8-oxo-9-(3A5-trimethoxyphenyl)-5,5a,6,8,8a.9- hexahvdrofuror3'.4':6,71naphthor2,3-cnri.31dioxol-5-yl) nonanedioate PPP (41 mg, 0.10 mmol), DMAP (6 mg, 0.05 mmol) and azelaic acid (9 mg, 0.05 mmol) were weighed in a vial. Dry dichloromethane (1.5 ml_) was added followed by EDC-HCI (23 mg, 0.12 mmol) at room temperature. The reaction mixture was stirred for three days. More dichloromethane was added and the solution was washed with 0.1 M HCI, saturated NaHC03 and brine. The crude product (55 mg) was purified by flash chromatography using Methanol: dichloromethane 1 : 25 to give the title product in 22 mg yield and 94% purity according to LCMS (ACE 3 C8, 50 x 3.0 mm, 10% to 97% acetonitrile in 3 min in 0.1 % TFA in water, 1 mUmin), MS ESI+ m/z 397, rt 2.720. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 3.5h; | 9 Example 9 (5R.5aR.8aS.9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5,5a,6,8,8a,9- hexahvdrofuror3'.4';6.71naphthor2.3-cnri.31dioxol-5-yl 2-((((9H-fluoren-9- yl)methoxy)carbonyl)amino)acetate Example 9 (5R.5aR.8aS.9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5,5a,6,8,8a,9- hexahvdrofuror3'.4';6.71naphthor2.3-cnri.31dioxol-5-yl 2-((((9H-fluoren-9- yl)methoxy)carbonyl)amino)acetate PPP (82 mg, 0.20 mmol), DMAP (12 mg, 0.1 mmol) and FMOC-glycine (60 mg, 0.2 mmol) were dissolved in dry dichloromethane (3 mL) and EDC-HCI (52 mg, 0.26 mmol) was added at room temperature. The reaction mixture was stirred for 3.5 hours. Then more dichloromethane was added and the solution was washed with 0.1 M HCI, saturated NaHC03 and brine. The crude product (141 mg) was purified by flash chromatography using 2% methanol in dichloromethane to give the product in 45% yield (62 mg) and >99% purity according to LCMS (ACE 3 C8, 50 x 3.0 mm, 10% to 97% acetonitrile in 3 min in 0.1% TFA in water, 1 mL/min), MS ESI+ m/z 397, rt 2.588. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 6h; | 11 Example 11 (R>-f5R.5aR.8aS.9R)-8-oxo-9-f3.4.5-trimethoxyphenyl)-5,5a,6,8,8a.9- θΧΒΗνιΓθυΓθΓβ'^^β.ΤΙηΒρΗΗοΓΣ.Β-ΓΙ^ΙαοχοΙ-β-νΙ 2-((((9H-fluoren-9- yl)methoxy)carbonyl)amino)-3-methylbutanoate Example 11 (R>-f5R.5aR.8aS.9R)-8-oxo-9-f3.4.5-trimethoxyphenyl)-5,5a,6,8,8a.9- θΧΒΗνιΓθυΓθΓβ'^^β.ΤΙηΒρΗΗοΓΣ.Β-ΓΙ^ΙαοχοΙ-β-νΙ 2-((((9H-fluoren-9- yl)methoxy)carbonyl)amino)-3-methylbutanoate PPP (62 mg, 0.15 mmol), DMAP (9 mg, 0.08 mmol) and FMOC-valine (51 mg, 0.15 mmol) were weighed in a vial. Dry dichloromethane (2.25 ml_) was added followed by EDC-HCI (38 mg, 0.2 mmol) at room temperature. The reaction mixture was stirred for 6 hours. Then more dichloromethane was added and the solution was washed with 0.1 M HCI, saturated NaHC03 and brine. The crude product (117 mg) was purified by flash chromatography using 2% methanol in dichloromethane as eluent to give the product (96 mg) in 87% yield and in 94% purity LCMS (ACE 3 C8, 50 x 3.0 mm, 10% to 97% acetonitrile in 3 min in 0.1% TFA in water, 1 mlJmin), MS ESI+ m/z 397, rt 2.755. |
Tags: 477-47-4 synthesis path| 477-47-4 SDS| 477-47-4 COA| 477-47-4 purity| 477-47-4 application| 477-47-4 NMR| 477-47-4 COA| 477-47-4 structure
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
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P243 | Take precautionary measures against static discharge. |
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P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
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P285 | In case of inadequate ventilation wear respiratory protection. |
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P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
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P304 | IF INHALED: |
P305 | IF IN EYES: |
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P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
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P342 | If experiencing respiratory symptoms: |
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P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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