Enantioselective synthesis of (S)-vigabatrin®

SmI2‐Induced Umpolung of the CN Bond: First Reductive Conjugate Addition of Nitrones to α,β‐Unsaturated Esters

“…Similarly, the ( R )‐2,3‐ O ‐isopropylidene‐ D ‐glyceraldehyde‐derived nitrone14 added to ethyl acrylate with good diastereoselectivity (Table 1, entry 8) and yielded an important intermediate15, 16 for the synthesis of Vigabatrin,17 a potent and selective GABA‐transaminase inhibitor used for treatment and prevention of epilepsy. The relative stereochemistry displayed in the product in entry 8 of Table 1 was determined by reduction of the hydroxylamine and carbamoylation to give a known15a Boc‐protected γ‐amino ester (Scheme a).…”

Synthesis of enantiomeric spirooxazolines and spirooxazolidines by the regioselective ring closure of (–)-α-pinene-based aminodiols

“…[1][2][3][4][5][6][7] For example, some have been found to act as HIV protease inhibitors [1][2][3] and still others have been shown to exert renin inhibitor activity. 5,6 Aminodiols are also useful starting materials for the syntheses of oxazines or oxazolidines, depending upon which hydroxy group undergoes ring closure with the amino group.…”

Synthesis of γ‐Aminobutyric Acid Analogs

“…(S)-Vigabatrin (S)-(2) has been prepared via multistep syntheses employing Sharpless epoxidation of 5-phenylpent-2-en-1-ol [133] and Sharpless asymmetric aminohydroxylation of ethyl 6-hydroxyhex-2-enoate as the sole source of chirality [134], and the addition of alkyl 3-lithiopropiolates [135] or SmI 2 -catalyzed addition of methyl acrylate [136] to the nitrone of D-glyceraldehyde. The cyclopropane analog of vigabatrin, (AE)-g-amino-g-cyclopropylbutanoic acid, has been prepared in six steps via a Mannich reaction of malonic acid, cyclopropanecarbaldehyde, and ammonium acetate, and subsequent Arndt-Eistert homologation [137].…”