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CAS No. : | 510-30-5 | MDL No. : | MFCD00017295 |
Formula : | C30H48O4 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | YKOPWPOFWMYZJZ-PRIAQAIDSA-N |
M.W : | 472.70 | Pubchem ID : | 73309 |
Synonyms : |
|
Num. heavy atoms : | 34 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.9 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 4.0 |
Num. H-bond donors : | 3.0 |
Molar Refractivity : | 137.82 |
TPSA : | 77.76 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | Yes |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -4.3 cm/s |
Log Po/w (iLOGP) : | 3.52 |
Log Po/w (XLOGP3) : | 6.88 |
Log Po/w (WLOGP) : | 6.2 |
Log Po/w (MLOGP) : | 4.97 |
Log Po/w (SILICOS-IT) : | 4.96 |
Consensus Log Po/w : | 5.31 |
Lipinski : | 1.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 1.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.56 |
Log S (ESOL) : | -7.04 |
Solubility : | 0.0000432 mg/ml ; 0.0000000914 mol/l |
Class : | Poorly soluble |
Log S (Ali) : | -8.32 |
Solubility : | 0.00000224 mg/ml ; 0.0000000047 mol/l |
Class : | Poorly soluble |
Log S (SILICOS-IT) : | -5.3 |
Solubility : | 0.00237 mg/ml ; 0.00000502 mol/l |
Class : | Moderately soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 2.0 |
Synthetic accessibility : | 6.28 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
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 diethyl ether | ||
35 mg | In methanol; diethyl ether for 24h; | |
In methanol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium dichromate; sulfuric acid; acetic acid at 20℃; | ||
Multi-step reaction with 2 steps 1: dipyridine chromium(VI) oxide; sulfuric acid / 1,4-dioxane / 4 h / 100 °C 2: dipyridine chromium(VI) oxide; Jones reagent / acetone / 0.33 h / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99.8% | With pyridine at 105℃; for 24h; | 1 Example 1 Preparation of Compound 1 1.00 g (2.120 mmol) of echinocystic acid was weighed into a round bottom flask and 40 mL of pyridine was added. 20 ml of acetic anhydride, magnetically stirred at 105 ° C for 24 h, TLC detection with petroleum ether-ethyl acetate-formic acid (8:2:0.05),After the reaction is completed, Transfer to a beaker, add 100 mL of ice water, add dilute hydrochloric acid, The pH was adjusted to 4, stirred, filtered, and the filter cake was recrystallized from ethanol and dried to give Compound 1. Compound 1, white powder 1.180 g, yield 99.8%; mp: 156-158 ° C; |
With sodium acetate; acetic acid Erwaermen des mit Methanol versetzten Reaktionsgemisches; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.0 mg | With hydrogenchloride In 1,4-dioxane at 80℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
9 mg | With hydrogenchloride In 1,4-dioxane at 80℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With tetrabutylammomium bromide; potassium carbonate In dichloromethane; water Inert atmosphere; Reflux; | |
80% | With tetrabutylammomium bromide; potassium carbonate In dichloromethane; water at 50℃; for 12h; Inert atmosphere; | 1 To a 50 mL reaction flask containing 20mL of bromo sugar (194mg, 0.47mmol) in DCM were added 189mg (0.4mmol) EA, 138 mg K2CO3, 52 mg of tetra-n-butylammonium bromide, 2 mL of water. The reaction was stired at 50°C with reflux in N2 atmosphere. The reaction was stoped after 12 h. Monitored by TLC, eluent PE: AcOEt = 1: 1. The resultant was purified on chromatography column under elution conditions PE:AcOEt=2:1 to give 252mg of white solid compound 3β,16α-dihydroxy-olean-12-en-28-oic acid-28-O (2,3,4,6-tetra-O-acetyl-β-D-glucoside), yield 80%. 1H NMR (400 MHz, CDCl3): δ 5.54 (d, 1 H, J = 8.2Hz, Glc-1-H), 5.39 (t, 1 H, J = 3.2Hz, H12), 5.08-5.24 (m, 3H), 4.39 (br t, 1 H, H16), 4.25 (dd, 1 H, J = 4.4, 12.4Hz), 4.02 (dd, 1H, J = 2.1, 12.4Hz), 3.74-3.78 (m, 1H), 3.19 (dd, 1H, J = 4.2, 10.6Hz, H3), 2.97 (dd, 1 H, J = 4.0, 14.3Hz, H18), 2.05, 2.00, 2.00, 1.99 (s, each 3H, CH3CO), 1.32, 0.96, 0.92, 0.89, 0.88, 0.75, 0.70 (s, each 3H, H27, H23, H30, H25, H29, H26) H24). 13C NMR (100 MHz, CDCl3): δ 174.72 (C=O, C28), 170.53, 170.03, 169.38, 169.07, 141.88 (C13), 123.22 (C12), 91.56 (Glc-1-C), 78.84, 74.22, 72.68, 72.41, 69.91, 67.90, 61.44, 55.19, 48.79, 46.61, 46.03, 41.31, 40.40, 39.49, 38.68, 38.48, 36.93, 35.46, 35.14, 33.02, 32.62, 30.23, 30.17, 28.01, 27.12, 26.76, 24.45, 23.24, 20.62 (CH3CO), 20.50 (3C, 3 × CH3CO), 18.22, 17.01, 15.55, 15.43. ESI-HRMS (m/z) calcd for C44H66O13Na (M+Na+): 825.4396. Found 825.4387; C44H70O13N (M+NH4+): 820.4842. Found 820.48400. The compound was represented by the following Q1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 4h; | |
86% | With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; | |
86% | With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; Inert atmosphere; |
86% | With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 5h; Inert atmosphere; | General procedure A for the synthesis of 1-benzotriazolyl triterpene ester (8-10 and 23) General procedure: To a solution of triterpene BA, OA, EA, or UA (0.22 mmol) in THF (10 mL) was added TBTU (106 mg, 0.33 mmol) and DIPEA (0.12 mL, 0.66 mmol) at room temperature. The reaction mixture was stirred for 5 h under nitrogen. The solvent was removed in vacuo. The residue was dissolved with CH2Cl2 (15 mL), washed with brine (3 × 5 mL), dried with Na2SO4, filtered, and the solvent was removed in vacuo. The crude product was purified by flash chromatography. |
86% | With N-ethyl-N,N-diisopropylamine In tetrahydrofuran for 10h; | 3 Example 3 Synthesis of echinocystic acid-glycine The operation steps: echinocystic acid 485mg dissolved in 5mL of tetrahydrofuran,Add DIPEA (,N-diisopropylethylamine) 50mg,TBTU 560mg, after treatment for 10h, evaporated to dryness, column separation,520mg of a white solid was obtained with a yield of 86% b.The above white solid was added alanine 300 mg, DMF 5 mL,Sodium carbonate 100mg, reaction at room temperature overnight, add water after treatment,A white solid precipitated and was filtered to give 450 mg of a white solid. Yield 96% |
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 4h; | ||
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; | ||
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | Stage #1: echinocystic acid With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: benzyl chloride In N,N-dimethyl-formamide at 20℃; for 18h; chemoselective reaction; | 2.1 Olean-3β, 16α-dihydroxy-12-en-28-phenylmethoxycarbonyl (1) EA (472 mg, 1 mmol) was dissolved in DMF (15 mL), and potassium carbonate (276 mg, 2 mmol) was added. After 60 min of stirring at rt, the benzylchloride (190 mg, 1.5 mmol) was added, and string was continued for an additional 18 h. The mixture was poured into an ice cold solution of aq HCl (3.7%, 50 mL), and the white precipitate was filtered off. The crude product was purified by column chromatography to afford 1 as white solid (483 mg, 86%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31% | With tetrabutylammomium bromide; potassium carbonate In dichloromethane; water at 50℃; for 12h; Inert atmosphere; | 2 To a 50 mL reaction flask containing 20mL of bromo sugar (the unseparated mixture in the above step reaction) DCM solution were added 188.8mg (0.4mmol) of EA, 138mg of K2CO3, 51.52mg of tetra-n-butylammonium bromide, and 2mL of water, allowed to react at 50°C in N2 atmosphere with reflux. The reaction was stopped after 12 h. The reaction was monitored by TLC until the reaction was complete. Eluent PE: AcOEt = 1: 1. The resultant was purified on chromatography column under elution condition PE: AcOEt = 1: 1 to give 98.5mg of a white solid 3β,16α-dihydroxy-olean-12-en-28-oic acid -28-O-(2,3,4,6-tetra-O-acetyl-β-D- galactopyranoside), yield 31%. 1H NMR (400 MHz, CDCl3): δ 5.54(d, 1 H, J =8.4Hz, Gal-1-H), 5.40-5.44(m, 2H), 5.31 (t, 1 H, J =10.3Hz), 5.07(dd, 1 H, J =3.4, 10.4Hz), 4.39(br t, 1 H, H16), 4.10-4.15(m, 2H), 4.00(t, 1 H, J =6.7Hz), 3.22(dd, 1 H, J =4.1, 10.4Hz, H3), 3.00(d, 1 H, J =10.6Hz, H18), 2.17, 2.04, 2.02, 1.99(s, each 3H, CH3CO), 1.34, 0.99, 0.95, 0.92, 0.91, 0.78, 0.75(s, each 3H, CH3, H27, H23, H30, H25, H29, H26, H24). 13C NMR (100 MHz, CDCl3): δ 174.64(C=O, C28), 170.22, 170.07, 169.84, 169.25, 141.87(C13), 123.13(C12), 92.03 (Gal-1-C), 78.82, 74.06, 71.39, 70.70, 67.56, 66.69, 60.65, 55.22, 48.97, 46.64, 46.07, 41.36, 40.48, 39.53, 38.69, 38.49, 36.95, 35.50, 35.06, 33.04, 32.58, 30.19, 29.82, 28.01, 27.13, 26.76, 24.65, 23.26, 20.64, 20.55, 20.44, 18.22, 17.07, 15.55, 15.47.ES1-HRMS (m/z) calcd for C44H66O13Na (M+Na+): 825.4396. Found 825.4387; C44H70O13N (M+NH4+): 820.4842. Found 820.4839. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
114.3 mg | With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran at 20℃; for 24h; | 3 Preparation of 3β,16α-dihydroxy-olean-12-en-28-oic acid-28-N-(2,3,4,6-tetra-O-acetyl-β-D- galactoside) 150mg of EA was dissolved with 5mL THF, added with 65mg of EDC, allowed to react at room temperature for 0.5h with stirring, added with the above product, allowed to react at room temperature for 1d. The reaction was monitored by TLC until the reaction was complete. Eluent PE:AcOEt =1:1. The solvent was removed by rotary evaporation. The resultant was mixed with 30mL AcOEt to give a suspension, washed successively with 30mL of distilled water three times and with 30 mL of saturated brine. The organic layer was dried over anhydrous Na2SO4, and purified on silica gel column to give about 114.3 mg of a white solid, 53% total yield in the two steps. 1H NMR (400 MHz, CDCl3): δ 0.79, 0.80, 0.90, 0.91, 0.92, 0.99, 1.16, 2.00, 2.02, 2.05, 2.14 (11 × CH3), 0.72-2.17 (m, other aliphatic ring protons), 2.55 (brd, 1H, J = 9.9 Hz), 3.21 (dd,1 H, J = 3.6, 10.4 Hz), 3.97-4.13 (m, 3H), 5.03-5.18 (m, 3H), 5.41-5.43 (m, 1 H), 5.50 (brs, 1 H), 6.68 (d, 1 H, J = 9.0 Hz).13C NMR (100 MHz, CDCl3): δ 15.3, 15.5, 17.0, 18.2, 20.4, 20.5, 20.5, 20.7, 23.1, 23.4, 23.9, 25.4, 27.0, 27.1, 28.0, 30.5, 32.4 (2C), 32.8, 34.0, 36.8, 38.4, 38.6, 39.2, 41.2, 41.9, 46.3, 46.5, 47.4, 55.0, 60.6, 67.0, 68.2, 70.7, 71.6, 78.5, 78.7, 123.4, 143.6, 169.7, 169.9, 170.2, 171.0, 178.9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride In methanol at 80℃; for 6h; | Acid hydrolysis of compounds 1 and 2 General procedure: A 5 mg of each compound was refluxed separately with2 M HCl in MeOH (5 mL) at 80 C for 6 h in a water bath.The reaction mixture was evaporated, and the hydrolysateafter dilution with H2O (10 mL) was extracted with CHCl3(3 9 10 mL). The CHCl3 extracts were evaporated to affordthe aglycons, which were identified as echinocysticacid (m/z 472 by EIMS and its NMR data) from 1 and 2.The aqueous layer was neutralized with 2 N KOH solutionand concentrated to 1 mL under reduced pressure. Theconcentrated aqueous layer showed spots at the same Rf asglucose, xylose, arabinose and rhamnose for 1 and 2 onTLC silica gel (30:12:4 CHCl3:MeOH:H2O), 9 mL oflower layer and 1 mL of HOAc, and on PC (iso-PrOH:n-BuOH:H2O 7:1:2), using aniline hydrogen phthalate as a detecting reagent.Echinocystic acid: An amorphous solid from MeOH;EIMS m/z 472 [M]+; 1H NMR (DMSO-d6, 500 MHz) d5.20 (1H, brs, H-12), 4.30 (1H, brt, H-16), 3.00 (1H, dd,J = 11.0, 5.0 Hz, H-3), 1.30 (s, H3-27), 0.90 (s, H3-30),0.89 (s, H3-23), 0.85 (s, H3-25), 0.83 (s, H3-29), 0.68 (s,H3-26), 0.67 (s, H3-24); 13C NMR data (DMSO-d6,125 MHz) d 177.0 (C-28), 144.1 (C-13), 121.2 (C-12), 76.8(C-3), 72.9 (C-16), 54.8 (C-5), 47.3 (C-17), 46.3 (C-19),46.2 (C-9), 41.0 (C-14), 40.0 (C-18), 38.3 (C-4), 39.1(C-8), 38.1 (C-1), 36.5 (C-10), 34.7 (C-15), 35.1 (C-21),32.8 (C-29), 32.6 (C-7), 31.3 (C-22), 30.2 (C-20), 28.2(C-23), 26.9 (C-2), 26.4 (C-27), 24.1 (C-30), 22.7 (C-11),18.0 (C-6), 16.8 (C-26), 16.0 (C-24), 15.1 (C-25). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride In methanol at 80℃; for 6h; | Acid hydrolysis of compounds 1 and 2 General procedure: A 5 mg of each compound was refluxed separately with2 M HCl in MeOH (5 mL) at 80 C for 6 h in a water bath.The reaction mixture was evaporated, and the hydrolysateafter dilution with H2O (10 mL) was extracted with CHCl3(3 9 10 mL). The CHCl3 extracts were evaporated to affordthe aglycons, which were identified as echinocysticacid (m/z 472 by EIMS and its NMR data) from 1 and 2.The aqueous layer was neutralized with 2 N KOH solutionand concentrated to 1 mL under reduced pressure. The concentrated aqueous layer showed spots at the same Rf as glucose, xylose, arabinose and rhamnose for 1 and 2 onTLC silica gel (30:12:4 CHCl3:MeOH:H2O), 9 mL oflower layer and 1 mL of HOAc, and on PC (iso-PrOH:n-BuOH:H2O 7:1:2), using aniline hydrogen phthalate as a detecting reagent.Echinocystic acid: An amorphous solid from MeOH;EIMS m/z 472 [M]+; 1H NMR (DMSO-d6, 500 MHz) d5.20 (1H, brs, H-12), 4.30 (1H, brt, H-16), 3.00 (1H, dd,J = 11.0, 5.0 Hz, H-3), 1.30 (s, H3-27), 0.90 (s, H3-30),0.89 (s, H3-23), 0.85 (s, H3-25), 0.83 (s, H3-29), 0.68 (s,H3-26), 0.67 (s, H3-24); 13C NMR data (DMSO-d6,125 MHz) d 177.0 (C-28), 144.1 (C-13), 121.2 (C-12), 76.8(C-3), 72.9 (C-16), 54.8 (C-5), 47.3 (C-17), 46.3 (C-19),46.2 (C-9), 41.0 (C-14), 40.0 (C-18), 38.3 (C-4), 39.1(C-8), 38.1 (C-1), 36.5 (C-10), 34.7 (C-15), 35.1 (C-21),32.8 (C-29), 32.6 (C-7), 31.3 (C-22), 30.2 (C-20), 28.2(C-23), 26.9 (C-2), 26.4 (C-27), 24.1 (C-30), 22.7 (C-11),18.0 (C-6), 16.8 (C-26), 16.0 (C-24), 15.1 (C-25). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With 2,6-dimethylpyridine In dichloromethane at 0℃; for 1h; | 7 Bis(silyl ether) of echinocystic acid (S14). Echinocystic acid S13 (18 mg, 38 μιηο, l.O equiv) was suspended in CH2C12 (10 mL) and cooled in an ice bath. 2,6-lutidine (71 μ, 0.61 mmol, 16 equiv) was then added followed by triethylsilyl trifluoromethanesulfonate (69 μ, 0.31 mmol, 8.0 equiv) and the reaction mixture was stirred at 0 °C for 1 h. After this time, the contents were washed with saturated NaHC03 (5 mL) and the aqueous phase was extracted with CH2C12 (2 x 10 mL). The combined organics were dried over Na2S04, filtered, and concentrated. The crude product t>7 was purified by silica gel chromatography (hexanes to 9: 1 hexanes/EtOAc) to afford S14 (25 mg, 94% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | Stage #1: echinocystic acid With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran at 20℃; for 0.5h; Stage #2: sulfanilamide In tetrahydrofuran at 20℃; | General procedure B for the synthesis of EA derivatives (9-12) General procedure: To the solution of EA (47 mg, 0.1 mmol) in 4 mL dry THF was added EDC (29 mg, 0.15 mmol). The reaction mixture was stirred at rt for 30 min and then corresponding amine was added. After completion (TLC) the solvent was removed under reduced pressure. The mixture was resolved in AcOEt and washed with water and brine twice. The organic layer was dried over Na2SO4, then filtered and concentrated. The crude product was purified by column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | Stage #1: echinocystic acid With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran at 20℃; for 0.5h; Stage #2: 4-morpholino-4-yl-phenylamine In tetrahydrofuran at 20℃; | General procedure B for the synthesis of EA derivatives (9-12) General procedure: To the solution of EA (47 mg, 0.1 mmol) in 4 mL dry THF was added EDC (29 mg, 0.15 mmol). The reaction mixture was stirred at rt for 30 min and then corresponding amine was added. After completion (TLC) the solvent was removed under reduced pressure. The mixture was resolved in AcOEt and washed with water and brine twice. The organic layer was dried over Na2SO4, then filtered and concentrated. The crude product was purified by column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37% | Stage #1: echinocystic acid With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran at 20℃; for 0.5h; Stage #2: NH-pyrazole In tetrahydrofuran at 20℃; | General procedure B for the synthesis of EA derivatives (9-12) General procedure: To the solution of EA (47 mg, 0.1 mmol) in 4 mL dry THF was added EDC (29 mg, 0.15 mmol). The reaction mixture was stirred at rt for 30 min and then corresponding amine was added. After completion (TLC) the solvent was removed under reduced pressure. The mixture was resolved in AcOEt and washed with water and brine twice. The organic layer was dried over Na2SO4, then filtered and concentrated. The crude product was purified by column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | Stage #1: echinocystic acid With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran at 20℃; for 0.5h; Stage #2: 1,2,4-Triazole In tetrahydrofuran at 20℃; | General procedure B for the synthesis of EA derivatives (9-12) General procedure: To the solution of EA (47 mg, 0.1 mmol) in 4 mL dry THF was added EDC (29 mg, 0.15 mmol). The reaction mixture was stirred at rt for 30 min and then corresponding amine was added. After completion (TLC) the solvent was removed under reduced pressure. The mixture was resolved in AcOEt and washed with water and brine twice. The organic layer was dried over Na2SO4, then filtered and concentrated. The crude product was purified by column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.33 g | With triethylamine In dichloromethane at 20℃; for 24h; Cooling with ice; | 4 Example 4 (3,16-p methyl benzoyl) echinocystic acid (compound 3) preparation of echinocystic acid 0.47g, soluble in 25mlCH 2 Cl 2 in, slowly dropping under ice bath to methyl benzoyl chloride 2 ml, then adding triethylamine 2 ml, stirring reaction under the normal temperature condition 24h, to be the reaction is complete, pressure reducing and recovering the solvent, drying, to obtain the crude product. The crude product is recrystallized with dichloromethane-petroleum ether, separation and purification with silica gel column (petroleum ether: ethyl acetate = 5:1), to obtain white powdery crystalline 0.33 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.28 g | With triethylamine In dichloromethane at 20℃; for 24h; Cooling with ice; | 5 Example 5 (3,16-di-2-thenoyl) echinocystic acid (compound 4) preparation of echinocystic acid 0.47g, soluble in 25mlCH 2 Cl 2 in, slowly dropping under ice bath 2-thiophene-formyl chloride 2 ml, then adding triethylamine 2 ml, stirring reaction under the normal temperature condition 24h, to be the reaction is complete, pressure reducing and recovering the solvent, drying, to obtain the crude product. The crude product is recrystallized with dichloromethane-petroleum ether, separation and purification with silica gel column (petroleum ether: ethyl acetate = 5:1), to obtain white powdery crystalline 0.28 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.39 g | With triethylamine In dichloromethane at 20℃; for 24h; Cooling with ice; | 6 Example 6 (3,16-bis trifluoromethyl methyl benzoyl) echinocystic acid (compound 5) preparation of echinocystic acid 0.47g, soluble in 25mlCH 2 Cl 2 in, slowly dropping under ice bath to the trifluoromethyl benzoyl chloride 2 ml, then adding triethylamine 2 ml, stirring reaction under the normal temperature condition 24h, to be the reaction is complete, pressure reducing and recovering the solvent, drying, to obtain the crude product. The crude product is recrystallized with dichloromethane-petroleum ether, separation and purification with silica gel column (petroleum ether: ethyl acetate = 5:1), to obtain white powdery crystalline 0.39 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.43 g | With triethylamine In dichloromethane at 20℃; for 24h; Cooling with ice; | 7 Example 7 (3,16-b to paradichlorbenzene Carbamoyl) echinocystic acid (compound 6) preparation of echinocystic acid 0.47g, soluble in 25mlCH 2 Cl 2 in, slowly dropping under ice bath to paradichlorbenzene formyl chloride 2 ml, then adding triethylamine 2 ml, stirring reaction under the normal temperature condition 24h, to be the reaction is complete, pressure reducing and recovering the solvent, drying, to obtain the crude product. The crude product is recrystallized with dichloromethane-petroleum ether, separation and purification with silica gel column (petroleum ether: ethyl acetate = 5:1), to obtain white powdery crystalline 0.43 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.29 g | With triethylamine In dichloromethane at 20℃; for 24h; Cooling with ice; | 8 Example 8 (3,16-b 2-phenyl-butyryl) echinocystic acid (compound 7) preparation of echinocystic acid 0.47g, soluble in 25mlCH 2 Cl 2 in, slowly dropping under ice bath 2-phenyl-butyrylchlorine 2 ml, then adding triethylamine 2 ml, stirring reaction under the normal temperature condition 24h, to be the reaction is complete, pressure reducing and recovering the solvent, drying, to obtain the crude product. The crude product is recrystallized with dichloromethane-petroleum ether, separation and purification with silica gel column (petroleum ether: ethyl acetate = 5:1), to obtain white powdery crystalline 0.29 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.25 g | With triethylamine In dichloromethane at 20℃; for 24h; Cooling with ice; | 9 Example 9 (3,16-di -3,5-dimethyl-benzoyl) echinocystic acid (compound 8) preparation of echinocystic acid 0.47g, soluble in 25mlCH 2 Cl 2 in, slowly dropping under ice bath 3,5-dimethyl-benzoyl chloride 2 ml, then adding triethylamine 2 ml, stirring reaction under the normal temperature condition 24h, to be the reaction is complete, pressure reducing and recovering the solvent, drying, to obtain the crude product. The crude product is recrystallized with dichloromethane-petroleum ether, separation and purification with silica gel column (petroleum ether: ethyl acetate = 5:1), to obtain white powdery crystalline 0.25 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.35 g | With triethylamine In dichloromethane at 20℃; for 24h; Cooling with ice; | 2 Example 2 (3,16-di-benzoyl) echinocystic acid (compound 1) preparation of echinocystic acid 0.47g, soluble in 25mlCH 2 Cl 2 in, slowly dropping benzoyl chloride under ice bath 2 ml, then adding triethylamine 2 ml, stirring reaction under the normal temperature condition 24h, to be the reaction is complete, pressure reducing and recovering the solvent, drying, to obtain the crude product. The crude product is recrystallized with dichloromethane-petroleum ether, separation and purification with silica gel column (petroleum ether: ethyl acetate = 5:1), to obtain white powdery crystalline 0.35 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.38 g | With triethylamine In dichloromethane at 20℃; for 24h; Cooling with ice; | 3 Example 3 (3,16-di-O-methyl benzoyl) echinocystic acid (compound 2) preparation of echinocystic acid 0.47g, soluble in 25mlCH 2 Cl 2 in, slow instillment neighbour methyl benzoyl chloride under ice bath 2 ml, then adding triethylamine 2 ml, stirring reaction under the normal temperature condition 24h, to be the reaction is complete, pressure reducing and recovering the solvent, drying, to obtain the crude product. The crude product is recrystallized with dichloromethane-petroleum ether, separation and purification with silica gel column (petroleum ether: ethyl acetate = 5:1), to obtain white powdery crystalline 0.38 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 33.2% 2: 12.3% | With sulfuric acid; dipyridine chromium(VI) oxide In 1,4-dioxane at 100℃; for 4h; | 2.1. Synthesis of auriculatone (A) and maragenin I (M) Echinocystic acid (0.21 mmol) was dissolved in dioxane (10 mL) at room temperature, and Collins reagent (0.56 mmol) and sulfuric acid (2 mol/L) were successively added into the solution with strong stirring, then the mixture was heated to 100 °C for 4 h. Once the reaction was finished, the solvent was evaporated under vacuum, producing a residue which was further dissolved in 20 mL of water and extracted with chloroform (3 × 20 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography (n-hexane/ethyl acetate 8:1), affording auriculatone (33.2%) and maragenin I (12.3%). Auriculatone, white solid, mp: 210-211 °C; HPLC purity: 99.1%; ESI-MS m/z: 427.3584 [M+H]+; 1H-NMR (400 MHz, CDCl3) δ: 0.77 (s, 3H), 0.84 (s, 3H), 0.88 (s, 3H), 0.90 (s, 3H), 0.92 (s, 3H), 0.98 (s, 3H), 1.16 (s, 3H), 2.56(d, J =14.1 Hz, 1H), 2.57 (s, 1H), 2.88 (m, 1H), 3.22 (br, 1H), 5.46 (s, 1H); 13C-NMR (100 MHz, CDCl3) δ: 15.4, 15.7, 17.6, 18.3, 21.0, 23.4, 27.0, 27.2, 28.2, 31.0, 32.8, 33.4, 34.4, 37.1, 38.4, 38.8, 39.5, 44.8, 46.5, 46.8, 46.9, 47.2, 47.5, 55.3, 78.9 (C-3), 122.6 (C-12), 142.6 (C-13), 214.8 (C-16). Maragenin I, white solid, mp: 209-211 °C; HPLC purity: 98.9%; ESI-MS m/z: 427.3562 [M+H]+; 1H-NMR (400 MHz, CDCl3) δ: 0.78 (s, 3H), 0.84 (s, 3H), 0.87 (s, 3H), 0.92 (s, 3H), 0.95 (s, 3H), 0.98 (s, 3H), 1.01 (s, 3H), 2.52 (d, J = 15.5 Hz, 1H), 3.22 (dd, J = 11.0, 4.3 Hz,1H), 5.46 (s, 1H); 13C-NMR (100 MHz, CDCl3) δ: 15.4, 15.5, 16.8, 18.5, 23.3, 23.4, 24.8, 25.5, 27.2, 28.1, 30.6, 33.0, 33.2, 36.9, 37.3, 38.2, 38.4, 38.6, 38.8, 42.8, 42.9, 44.1, 47.3, 49.6, 55.5, 78.9 (C-3), 117.7 (C-12), 142.4 (C-13), 215.7 (C-16). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 5h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With copper(II) sulfate; sodium L-ascorbate In dichloromethane; water at 20℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; water; at 85℃; for 2h; | General procedure: Each saponin (2 mg) was hydrolyzed with 2 ml of 2 M HCl at 85 C during 2 h. After cooling, the solvent was removed under reduced pressure. The sugar mixture was extracted from the aqueous phase (10 ml) and washed with CH2Cl2 (3 × 5 ml). The combined CH2Cl2 extracts were washed with water to give after evaporation the aglycone moiety, which was compared with an authentic standard sample by Co-TLC. The sugars were first analyzed by TLC over silica gel (CHCl3-MeOH-H2O, 8:5:1) by comparison with standard samples. The absolute configuration of each monosaccharide was determined from GC-MS analysis of their trimethylsilylated derivatives by comparison with authentic samples using the method previously described (Chaabi et al., 2010). The following sugars were detected: D-glucose, 2-(acetamido)-2-deoxy-D-glucose, D-xylose, L-arabinose, and D-apiose. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; water; at 85℃; for 2h; | General procedure: Each saponin (2 mg) was hydrolyzed with 2 ml of 2 M HCl at 85 C during 2 h. After cooling, the solvent was removed under reduced pressure. The sugar mixture was extracted from the aqueous phase (10 ml) and washed with CH2Cl2 (3 × 5 ml). The combined CH2Cl2 extracts were washed with water to give after evaporation the aglycone moiety, which was compared with an authentic standard sample by Co-TLC. The sugars were first analyzed by TLC over silica gel (CHCl3-MeOH-H2O, 8:5:1) by comparison with standard samples. The absolute configuration of each monosaccharide was determined from GC-MS analysis of their trimethylsilylated derivatives by comparison with authentic samples using the method previously described (Chaabi et al., 2010). The following sugars were detected: D-glucose, 2-(acetamido)-2-deoxy-D-glucose, D-xylose, L-arabinose, and D-apiose. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; water; at 85℃; for 2h; | General procedure: Each saponin (2 mg) was hydrolyzed with 2 ml of 2 M HCl at 85 C during 2 h. After cooling, the solvent was removed under reduced pressure. The sugar mixture was extracted from the aqueous phase (10 ml) and washed with CH2Cl2 (3 × 5 ml). The combined CH2Cl2 extracts were washed with water to give after evaporation the aglycone moiety, which was compared with an authentic standard sample by Co-TLC. The sugars were first analyzed by TLC over silica gel (CHCl3-MeOH-H2O, 8:5:1) by comparison with standard samples. The absolute configuration of each monosaccharide was determined from GC-MS analysis of their trimethylsilylated derivatives by comparison with authentic samples using the method previously described (Chaabi et al., 2010). The following sugars were detected: D-glucose, 2-(acetamido)-2-deoxy-D-glucose, D-xylose, L-arabinose, and D-apiose. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride In 1,4-dioxane; water at 95℃; for 0.5h; Inert atmosphere; | Acid hydrolysis and HPLC analysis General procedure: According tothe reported method.4) Briefly, each solution of 1-4 (5 mg) in 0.2 M HCl (dioxane-H2O 1:1, 3 mL) washeated at 95 °C for 30 min under argon. After cooling,the mixture was neutralized by passage through anAmberlite-IRA-93ZU (Organo, Tokyo, Japan) columnand chromatographed (Diaion HP-20, 40% MeOH followedby Me2CO-EtOH 1:1) to give aglycone fractions(2.5 mg) and a sugar fraction (1.7 mg). The aglyconewas identified as machaerinic acid (a25D + 81.7°; c 0.5,MeOH) in compound 1, echinocystic acid (a25D + 32°;c 0.6, MeOH) in compound 2, and oleanolic acid(a25D + 76°; c 0.6, MeOH) in compounds 3 and 4.After the sugar fraction was passed through a Sep-Pak-C18 cartridge (Waters, Milford, MA, USA; with 40%MeOH) and Toyopak-IC-SP-M-cartridge (Tosoh; with40% MeOH), it was analyzed by HPLC (MeCN-H2O17: 3, flow rate, 0.9 mL min-1; detection, refractiveindex (RI) and optical rotation (OR): 7.79 (L-rhamnose, negative OR); 9.35 (L-arabinose, positive OR), 9.73(D-xylose, positive OR). 15.37 (D-glucose, positiveOR); 14.65 (D-galactose, positive OR). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | Stage #1: echinocystic acid With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran at 20℃; for 0.5h; Stage #2: C8H13N3 In tetrahydrofuran at 20℃; for 24h; | 2.4 Fourth Step: N-Propargyl-N- (3-methyl-3H-bislazin-3-propyl) -3β, 16α-dihydroxy-Synthesis of 12-ene-28-amide. Add 80mg EA (0.17) in 6mL double distilled THF, add 50mg EDC (0.25mmol) at room temperature, stir for 0.5h, add excess 3 'of intermediate, react at room temperature for 1d till TLC to complete EA reaction.The solvent was evaporated and the remaining viscous mixture was suspended with 30 mL of ethyl acetate, washed with distilled water (20 mL x 3) and once with 30 mL of brine.The organic phase was dried over anhydrous sodium sulfate, filtered and subjected to silica gel column chromatography (petroleum ether / ethyl acetate 3/1 v / v) to give 78 mg of a white solid productN-propargyl-N- (3-methyl-3H-bis-aziridin-3-propyl) -3β, 16α-dihydroxycholidino-12-en-28-amide,Yield 76%, mp 99.1-101.0 ° C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 24h; | 1.1 The first step: Synthesis of intermediate 1. Echinocystic acid EA (1 g, 2.2 mmol), benzyl bromide (562 mg, 3.3 mmol) was dissolved with 30 mL of DMF followed by potassium carbonate (604 mg, 4.4 mmol). Stir vigorously at 60 ° C for 24h. The DMF was distilled off in vacuo and the product was purified on a silica gel column to give Intermediate 1 (1.1 g, 89% yield). |
With anhydrous sodium carbonate In N,N-dimethyl-formamide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With tetrabutylammomium bromide; potassium carbonate In dichloromethane at 50℃; for 12h; Inert atmosphere; | 1 Towards 20 mL of brominated sugar(194mg, 0.47mmol)Add DCM solution to 50mL reaction flaskEA 189 mg (0.4 mmol), K2CO3 138 mg,Tetra-n-butylammonium bromide 52mg, water 2mL,The reaction was refluxed at 50°C and protected with N2.After 12 hours, the reaction was stopped. TLC monitoring,The developing agent PE:EA=1:1. Column separation and purificationElution conditions PE:EA=2:1252 mg of a white solid compound was obtained in a yield of 80%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | Stage #1: echinocystic acid With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 3h; Stage #2: Propargylamine In tetrahydrofuran for 0.5h; | 2.a Example 2 Syntheses of echinocystic acid-glucose derivatives by click reaction (a) Dissolve 472 mg (1 mmol) EA in 10 mL THF.TBTU 385 mg (1.2 mmol) and DIEA 0.4 mL (2.4 mmol) were added,After stirring for 3h at room temperature until the EA reaction is complete,Propargylamine 0.13 mL (2 mmol) was added to the system.Continue the reaction for 0.5h until the reaction is complete. The precipitate was filtered off and the filtrate was concentrated under reduced pressure.Stir silica gel column chromatography with petroleum ether:ethyl acetate=2:1 to obtain 458 mg of product 2 as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In tetrahydrofuran | 8 Example 8 Synthesis of 28- Glucosamine - echinocystic acid The echinocystic acid 150mg, dissolved with 6mL of THF,Add 100 mg of glucosamine (excess),TBTU 100mg, DIPEA 20mg, overnight reaction, separation: ethyl acetate/methanol = 12:1,Eluting to a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With potassium carbonate In N,N-dimethyl-formamide at 20℃; Inert atmosphere; | Synthesis of 6A-(3β,16α-dihydroxy-olean-12-en-28-oate)-per-O-benzylated β-CD (9) To a solution of bromide 7 (107 mg, 0.036 mmol) in 2 mL DMF, EA (34.0 mg, 0.072 mmol) and K2CO3 (19.9 mg, 0.14 mmol) were added. The reaction mixture was stirred at room temperature under nitrogen until the starting material 7 was not observed by TLC detection. The reaction mixture was concentrated in vacuo and the residue was purified by column chromatography on silica gel (eluent: petroleum ether/EtOAc = 2:1) to give compound 9 (75.0 mg, 62%) as a white foam. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; | To a solution of mono 6A-deoxy-6A-amino-beta-CD (113 mg, 0.10 mmol) in DMF (5 mL) was added EDC (43 mg, 0.23 mmol) and DMAP (4.0 mg, 0.03 mmol). The resulting solution was stirred at room temperature for 0.5 h and echinocystic acid (71 mg, 0.15 mmol) was added. The resulting solution was stirred until the beta-CD was completely consumed as determined by thin-layer chromatography (TLC). The suspension was evaporated and purified by RP flash chromatography (eluent: methanol/H2O = 4:1) to afford 16 as a white solid in 43percent yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With dmap; 1,2-dichloro-ethane In dichloromethane at 20℃; for 1h; | 4.2.1. General procedure for amide bond formation reaction(method A) General procedure: To a solution of the carboxyl compound (1.0 equiv.) in DCM, EDC(1.6 equiv.) and DMAP (0.25 equiv.) were added slowly. Then the amino compound (1.2 equiv.) was added to the mixture. The reactionmixture was stirred at room temperature for 1 h and thenwashed with saturated salt solution (50 mL 3). The organic layerwas collected, dried over Na2SO4, filtered and concentrated. Theresidue was purified by column chromatography over silica gel. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With dmap; 1,2-dichloro-ethane In dichloromethane at 20℃; for 1h; | 4.2.1. General procedure for amide bond formation reaction(method A) General procedure: To a solution of the carboxyl compound (1.0 equiv.) in DCM, EDC(1.6 equiv.) and DMAP (0.25 equiv.) were added slowly. Then the amino compound (1.2 equiv.) was added to the mixture. The reactionmixture was stirred at room temperature for 1 h and thenwashed with saturated salt solution (50 mL 3). The organic layerwas collected, dried over Na2SO4, filtered and concentrated. Theresidue was purified by column chromatography over silica gel. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With dmap; 1,2-dichloro-ethane In dichloromethane at 20℃; for 1h; | 4.2.1. General procedure for amide bond formation reaction(method A) General procedure: To a solution of the carboxyl compound (1.0 equiv.) in DCM, EDC(1.6 equiv.) and DMAP (0.25 equiv.) were added slowly. Then the amino compound (1.2 equiv.) was added to the mixture. The reactionmixture was stirred at room temperature for 1 h and thenwashed with saturated salt solution (50 mL 3). The organic layerwas collected, dried over Na2SO4, filtered and concentrated. Theresidue was purified by column chromatography over silica gel. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With dmap; 1,2-dichloro-ethane In dichloromethane at 20℃; for 1h; | 4.2.1. General procedure for amide bond formation reaction(method A) General procedure: To a solution of the carboxyl compound (1.0 equiv.) in DCM, EDC(1.6 equiv.) and DMAP (0.25 equiv.) were added slowly. Then the amino compound (1.2 equiv.) was added to the mixture. The reactionmixture was stirred at room temperature for 1 h and thenwashed with saturated salt solution (50 mL 3). The organic layerwas collected, dried over Na2SO4, filtered and concentrated. Theresidue was purified by column chromatography over silica gel. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With dmap; 1,2-dichloro-ethane In dichloromethane at 20℃; for 1h; | 4.2.1. General procedure for amide bond formation reaction(method A) General procedure: To a solution of the carboxyl compound (1.0 equiv.) in DCM, EDC(1.6 equiv.) and DMAP (0.25 equiv.) were added slowly. Then the amino compound (1.2 equiv.) was added to the mixture. The reactionmixture was stirred at room temperature for 1 h and thenwashed with saturated salt solution (50 mL 3). The organic layerwas collected, dried over Na2SO4, filtered and concentrated. Theresidue was purified by column chromatography over silica gel. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With dmap; 1,2-dichloro-ethane In dichloromethane at 20℃; for 1h; | 4.2.1. General procedure for amide bond formation reaction(method A) General procedure: To a solution of the carboxyl compound (1.0 equiv.) in DCM, EDC(1.6 equiv.) and DMAP (0.25 equiv.) were added slowly. Then the amino compound (1.2 equiv.) was added to the mixture. The reactionmixture was stirred at room temperature for 1 h and thenwashed with saturated salt solution (50 mL 3). The organic layerwas collected, dried over Na2SO4, filtered and concentrated. Theresidue was purified by column chromatography over silica gel. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With dmap; 1,2-dichloro-ethane In dichloromethane at 20℃; for 1h; | 4.2.1. General procedure for amide bond formation reaction(method A) General procedure: To a solution of the carboxyl compound (1.0 equiv.) in DCM, EDC(1.6 equiv.) and DMAP (0.25 equiv.) were added slowly. Then the amino compound (1.2 equiv.) was added to the mixture. The reactionmixture was stirred at room temperature for 1 h and thenwashed with saturated salt solution (50 mL 3). The organic layerwas collected, dried over Na2SO4, filtered and concentrated. Theresidue was purified by column chromatography over silica gel. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With dmap; 1,2-dichloro-ethane In dichloromethane at 20℃; for 1h; | 4.2.1. General procedure for amide bond formation reaction(method A) General procedure: To a solution of the carboxyl compound (1.0 equiv.) in DCM, EDC(1.6 equiv.) and DMAP (0.25 equiv.) were added slowly. Then the amino compound (1.2 equiv.) was added to the mixture. The reactionmixture was stirred at room temperature for 1 h and thenwashed with saturated salt solution (50 mL 3). The organic layerwas collected, dried over Na2SO4, filtered and concentrated. Theresidue was purified by column chromatography over silica gel. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With Gliocladium roseum CGMCC 3.3657 In ethanol for 288h; Microbiological reaction; | 3.4. Biocatalysis of EA and isolation of transformation products The preparative scale biotransformation of EA by G. roseum CGMCC 3.3657 was carried outin twelve 1000 mL flasks of liquid potato media. 500 mg of substrate in total (suspended in24 mL ethanol) were added into the media after 2 days. The reaction was continued for10 days after incubation of substrate, and then broth, and mycelia were extracted threetimes by EtOAc. The crude extract 1.78 g was separated on a silica gel (25 g) column and was eluted with petroleum ether/THF from 20:1 to 1:1 to afford nine fractions. Fraction F waspurified by silica gel column with petroleum ether/CHCl3 from 2:3 to 1:9 to afford 2 (13.6 mg).Fraction E was further purified by preparative HPLC with MeOH: H2O = 75:25 at 3 mL/minand 3 (10.1 mg) was obtained.Compound 2: 4, 16α-dihydroxy-3,4-seco-olean-12-en-3,28-dioic acid, (1R,2R,4aR,4bS,6R,6aR)-1-(2-carboxyethyl)-6-hydroxy-2-(2-hydroxypropan-2-yl)-1,4a,4b,9,9-penta methyl-1,2,3,4,4a,4b,5,6,6a,7,8,9,10,10a,12,12a-hexadecahydrochrysene-6a-carboxylic acidWhite powder, mp 329-331 °C, [α]20 D + 12.4° (c = 1.53 × 10-3, EtOH), HR-ESI-MS: 503.3387([M-H]-) (calcd 503.3373), 539.3156 ([M + Cl]-), 1007.6840 [2 M-H]-, 1H NMR and 13C NMR werein Table S1.Compound 3: 16α-hydroxy, A-homo-3α-oxa-olean-12-en-3-one-28-oic acid, (7aR,7bS,9R,9aR,15bR)-9-hydroxy-5,5,7a,7b,12,12,15b-heptamethyl-3-oxo-1,2,3,5,5a,6,7,7a,7b,8,9,9a,10,11, 12,13,13a,15,15a,15b-icosahydrochryseno[2,1-c]oxepine-9a-carboxylic acidWhite powder, mp 318-323 °C, [α]20 D + 52.9° (c = 3.37 × 10-3, EtOH), HR-ESI-MS: 485.3285([M-H]-) (calcd 485.3267), 1H NMR and 13C NMR were in Table S1. |
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