Enzyme Catalysis in the Synthesis of Active Pharmaceutical Ingredients

Goswami, Animesh

doi:10.1002/9780470627303.ch5

Cited by 1 publication

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References 111 publications

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“…To this end, the enzymatic reduction of α-bromoketone 8 to α-bromohydrin 14 followed by the facile formation of epoxide 15 now became our focus. , At the beginning, we explored the enzyme reduction of ( S )-ethyl 1-(2-(4-cyanophenyl)-2-oxoethyl)piperidine-3-carboxylate hydrobromide 9 to the chiral alcohol 10 in the original synthesis of BMS-960 (Scheme ). The initial screening of a number of both NADH- and NADPH-dependent ketoreductases proved to be very encouraging.…”

Section: Resultsmentioning

confidence: 99%

Regioselective Epoxide Ring Opening for the Stereospecific Scale-Up Synthesis of BMS-960, A Potent and Selective Isoxazole-Containing S1P₁ Receptor Agonist

Hou

Zhang

Chen

et al. 2017

Org. Process Res. Dev.

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This article presents a stereospecific scale-up synthesis of (S)-1-((S)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylic acid (BMS-960), a potent and selective isoxazole-containing S1P1 receptor agonist. The process highlights an enzymatic reduction of α-bromoketone toward the preparation of (S)-bromo alcohol, a key precursor of (S)-4-(oxiran-2-yl)benzonitrile. A regioselective and stereospecific epoxide ring-opening reaction was also optimized along with improvements to 1,2,4-oxadiazole formation, hydrolysis, and crystallization. The improved process was utilized to synthesize batches of BMS-960 for Ames testing and other toxicological studies.

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Section: Resultsmentioning

confidence: 99%

Regioselective Epoxide Ring Opening for the Stereospecific Scale-Up Synthesis of BMS-960, A Potent and Selective Isoxazole-Containing S1P₁ Receptor Agonist

Hou

Zhang

Chen

et al. 2017

Org. Process Res. Dev.

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Enzyme Catalysis in the Synthesis of Active Pharmaceutical Ingredients

Cited by 1 publication

References 111 publications

Regioselective Epoxide Ring Opening for the Stereospecific Scale-Up Synthesis of BMS-960, A Potent and Selective Isoxazole-Containing S1P₁ Receptor Agonist

Regioselective Epoxide Ring Opening for the Stereospecific Scale-Up Synthesis of BMS-960, A Potent and Selective Isoxazole-Containing S1P₁ Receptor Agonist

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Enzyme Catalysis in the Synthesis of Active Pharmaceutical Ingredients

Cited by 1 publication

References 111 publications

Regioselective Epoxide Ring Opening for the Stereospecific Scale-Up Synthesis of BMS-960, A Potent and Selective Isoxazole-Containing S1P1 Receptor Agonist

Regioselective Epoxide Ring Opening for the Stereospecific Scale-Up Synthesis of BMS-960, A Potent and Selective Isoxazole-Containing S1P1 Receptor Agonist

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Regioselective Epoxide Ring Opening for the Stereospecific Scale-Up Synthesis of BMS-960, A Potent and Selective Isoxazole-Containing S1P₁ Receptor Agonist

Regioselective Epoxide Ring Opening for the Stereospecific Scale-Up Synthesis of BMS-960, A Potent and Selective Isoxazole-Containing S1P₁ Receptor Agonist