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Chemical Structure| 52-52-8 Chemical Structure| 52-52-8
Chemical Structure| 52-52-8

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Cycloleucine is a specific inhibitor of S-adenosylmethionine-mediated methylation and also an antagonist at the glycine modulatory site of the NMDA receptor, with a Ki of 600 μM. Additionally, It is a competitive inhibitor of ATP in vitro, possessing anxiolytic and cell-inhibitory effects.

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Product Details of Cycloleucine

CAS No. :52-52-8
Formula : C6H11NO2
M.W : 129.16
SMILES Code : O=C(C1(CCCC1)N)O
MDL No. :MFCD00001381
InChI Key :NILQLFBWTXNUOE-UHFFFAOYSA-N
Pubchem ID :2901

Safety of Cycloleucine

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H312-H315-H319-H332-H335
Precautionary Statements:P262-P280-P301+P310-P304+P340-P305+P351+P338-P310

Application In Synthesis of Cycloleucine

* 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.

  • Downstream synthetic route of [ 52-52-8 ]

[ 52-52-8 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 501-53-1 ]
  • [ 52-52-8 ]
  • [ 17191-44-5 ]
YieldReaction ConditionsOperation in experiment
78% To a solution of 1-aminocyclopentanecarboxylic acid (3.0 g, 23.2 mmol) in 1:1 dioxane/water (60 mL), was slowly added Na2CO3 (12.3 g, 116 mmol) followed by benzyl chloroformate (3.6 mL, 25.5 mmol) and the mixture stirred overnight at RT. The reaction mixture was carefully acidified to pH=2 with 1M HCl then extracted with EtOAc (3*30 mL). The combined organic extracts were washed with brine (30 mL), dried (MgSO4), filtered and concentrated in vacuo to leave a pale yellow oil. LCMS and NMR showed the crude product to be a mixture of desired product and corresponding benzyl ester. The crude product was dissolved in 1:1 THF/water (60 mL) and treated with lithium hydroxide (2.67 g, 116 mmol). The mixture was stirred at RT overnight then washed with Et2O (3*30 mL), acidified to pH=2 and extracted with EtOAc (3*30 mL). The combined organic extracts were washed with brine (30 mL), dried (MgSO4), filtered and concentrated under reduced pressure to afford the title compound (4.76 g, 78%). LCMS: m/z 264 [M+H]+.
78% To a solution of 1-aminocyclopentanecarboxylic acid (3.0 g, 23.2 mmol) in 1 :1 dioxane / water (60 ml), was slowly added Na2CO3 (12.3 g, 116 mmol) followed by benzyl chloroformate (3.6 ml, 25.5 mmol) and the mixture stirred overnight at RT. The reaction mixture was carefully acidified to pH 2 with 1 M HCI then extracted with EtOAc (3 x 30 ml). The combined organic extracts were washed with brine (30 ml), dried (MgSO4), filtered and concentrated in vacuo to leave a pale yellow oil. LCMS and NMR showed the crude product to be a mixture of desired product and corresponding benzyl ester. The crude product was dissolved in 1 :1 THF / water (60 ml) and treated with lithium hydroxide (2.67 g, 116 mmol). The mixture was stirred at RT over night then washed with Et2O (3 x 30 ml), acidified to pH 2 and extracted with EtOAc (3 x 30 ml). The combined organic extracts were washed with brine (30 ml), dried (MgSO4), filtered and concentrated under reduced pressure to afford the title compound (4.76 g, 78%). LCMS: m/z 264 [M+H]+.
62% With sodium carbonate; In 1,4-dioxane; water; at 0 - 20℃; A solution of benzyl chloroformate (0.290 g, 1.1 mmol) in dioxane (2.5 cm3) was added dropwise to a solution of 1 -aminocyclopentanecarboxylic acid (Fluka) (0.2 g, 1.54 mmol) and sodium carbonate (0.490 g, 4.64 mmol) in water (5 cm3) at 0 C. Stirring was continued at room temperature overnight and the reaction mixture washed with ether. The aqueous layer was acidified with 2M hydrochloric acid, extracted with ethyl acetate, dried (Na2SO4), filtered and the solvent removed to afford carbamate 21 (0.253 g, 62%) as an oil which solidified on standing. Carbamate 21 was shown to be a 70:30 mixture of conformers by 1H NMR analysis (the ratio was estimated from the integration of the resonances at delta 5.31 and 7.29-7.40, assigned to the N-H protons of the major and minor conformers, respectively): mp 70-80 C (lit.1 82-86 C, ethyl acetate, petroleum ether); SH (400 MHz; CDCl3; Me4Si) 1.83 (4H, br s, 2 x cyclopentyl-H2), 2.04 (2H, br s, cyclopentyl-H2), 2.20-2.40 (2H, m, cyclopentyl- H2), 5.13 (2H, br s, OCH2Ph), 5.31 (0.7eta, br s, N-H) and 7.29-7.40 (5.3H, m, Ph and N-H*); deltac (100 MHz; CDCl3) 24.6 (CH2, cyclopentyl-C), 37.5 (CH2, cyclopentyl-C),' denotes resonance assigned to minor conformer. <n="31"/>66.0 (quat., cyclopentyl-C), 66.8 (CH2, OCH2Ph), 128.0 (CH, Ph), 128.1 (CH, Ph), 128.4 (CH, Ph), 136.1 (quat, Ph), 155.8 (quat., NCO2) and 179.5 (quat., CO2H).
62% With sodium carbonate; In 1,4-dioxane; water; at 0 - 20℃; N-Benzyloxycarbonyl-1-aminocyclopentane-1-carboxylic acid 21 A solution of benzyl CHLOROFORMATE (0.290 g, 1.1 mmol) in dioxane (2.5 CM3) was added dropwise to a solution of L-AMINOCYCLOPENTANECARBOXYLIC acid (Fluka) (0.2 g, 1.54 mmol) and sodium carbonate (0.490 g, 4.64 mmol) in water (5 CM3) at 0 C. Stirring was continued at room temperature overnight and the reaction mixture washed with ether. The aqueous layer was acidified with 2M hydrochloric acid, extracted with ethyl acetate, dried (NA2S04), filtered and the solvent removed to afford carbamate 21 (0.253 g, 62%) as an oil which solidified on standing. Carbamate 21 was shown to be a 70: 30 mixture of conformers by 1H NMR analysis (the ratio was estimated from the integration of the resonances at No. 5.31 and 7.29-7. 40, assigned to the N-H protons of the major and minor conformers, respectively): mp 70-80 C (lit. l 82-86 C, ethyl acetate, petroleum ether); IH (400 MHz; CDC13 ; Me4Si) 1.83 (4H, br s, 2 x CYCLOPENTYL-H2), 2.04 (2H, br s, cyclopentyl-H2), 2.20-2. 40 (2H, M, cyclopentyl- H2), 5.13 (2H, br s, OCH2Ph), 5.31 (0.7H, br s, N-H) and 7.29-7. 40 (5.3H, M, Ph and N-H*) ; DC (100 MHz; CDC13) 24.6 (CH2, cyclopentyl-C), 37.5 (CH2, cyclopentyl-C), 66.0 (quat. , cyclopentyl-C), 66.8 (CH2, OCH2PH), 128.0 (CH, Ph), 128.1 (CH, Ph), 128.4 (CH, Ph), 136.1 (quat, Ph), 155.8 (quat. , NC02) and 179.5 (quat. , CO2H).
62% With sodium carbonate; In 1,4-dioxane; water; at 0 - 20℃; N-Benzyloxycarbonyl-l-aminocyclopentane-l-carboxylic acid 21 A solution of benzyl chloroformate (0.290 g, 1.1 mmol) in dioxane (2.5 cm3) was added dropwise to a solution of l-aminocyclopentanecarboxylic acid (Fluka) (0.2 g, 1.54 mmol) and sodium carbonate (0.490 g, 4.64 mmol) in water (5 cm3) at 0 C. Stirring was continued at room temperature overnight and the reaction mixture washed with ether. The aqueous layer was acidified with 2M hydrochloric acid, extracted with ethyl acetate, dried (Na2SC>4), filtered and the solvent removed to afford carbamate 21 (0.253 g, 62%) as an oil which solidified on standing. Carbamate 21 was shown to be a 70:30 mixture of conformers by NMR analysis (the ratio was estimated from the integration of the resonances at 6 5.31 and 7.29-7.40, assigned to the N-H protons of the major and minor conformers, respectively): mp 70-80 C (lit.1 82-86 C, ethyl acetate, petroleum ether); < (400 MHz; CDC; Me4Si) 1.83 (4H, br s, 2 x cyclopentyl-H2), 2.04 (2H, br s, cyclopentyl-H2), 2.20-2.40 (2H, m, cyclopenty[-H2), 5.13 (2H, br s, OCiPh), 5.31 (0.7H, br s, N-H) and 7.29-7.40 (5.3H, m, Ph and N-H*); <5fc (100 MHz; CDC13) 24.6 (CH2, cyclopentyl-C), 37.5 (CH2, cyclopentyl-C), 66.0 (quat., cyclopentyl-C), 66.8 (CH2) OCH2Ph), 128.0 (CH, Ph), 128.1 (CH, Ph), 128.4 (CH, Ph), 136.1 (quat, Ph), 155.8 (quat, NC02) and 179.5 (quat., C02H).

 

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