A simple total synthesis of naturally occurring hydroxy-amino acids by enzymatic kinetic resolution

An Asymmetric, Chemo‐Enzymatic Synthesis of O‐Acetylcyanohydrins

“…Porcine pancreatic lipase, Candida rugosa lipase, Pseudomonas fluorescens lipase and Pseudomonas cepacia lipase, have all previously been used in the synthesis of optically active cyanohydrins, [23][24][25][26][27] but gave poor conversions and enantioselectivities with substrate 2. Rhizopus nevieus lipase was also totally unreactive towards compound 2 under the reaction conditions studied.…”

Medicinal Chemistry of α‐Hydroxy‐β‐Amino Acids

“…There are other interesting approaches to the synthesis of both isoserine enantiomers described by Andruszkiewicz in his review: in the multistep procedure described by Dureault et al, D-mannitol was employed as a starting material [9]; Pons et al used Sharpless asymmetric epoxidation of allyl alcohol [10]; Lu (S)-isoserine organic solvents using Candida cylindracea lipases (CCL) [11]; Nozaki et al synthesized L-and D-isoserine enantioselectively via asymmetric hydrogenation of 3-amino-2-oxopropanoate catalyzed by [RuCl(BINAP)benzene]Cl; [12] and many others [2].…”

“…This type of reaction is based on the dual role of an acid chloride as an activator of the aziridine ring and a provider of the nucleophile for the aziridine ring-opening, and results in acyclic b-amino-a-chlorocarbonyl product 10. Intermediate 10 is readily cyclized due to internal oxygen attack and replacement of the chloride (11). Compound 11, in the presence of a small amount of water or moisture in the air, hydrolyzes to yield 12.…”

Synthesis of γ‐Aminobutyric Acid Analogs

“…Isolation of the major isomer by recrystallization and cleavage of the chiral auxiliary yields the enantiomerically pure acid (195). Arndt-Eistert homologation yields the methyl ester (196). Reduction of the nitrile and acid hydrolysis afforded (R)- (197) in 65% overall yield [152].…”

“…Treatment of the residual O-acetyl cyanohydrin (S)- (277) with PPL gives the (S)-cyanohydrin (S)- (278). Reduction of the cyanohydrins affords enantiomerically pure (R)- (6) and (S)-(6) in good yields [196].…”