A new, short and efficient synthesis of both enantiomers of carnitine

Total Synthesis of Microsclerodermin E

“…The GABOB unit 10 was constructed from methyl ( R )‐3,4‐dihydroxybutanoate 9 9 (Scheme ). Selective tosylation10 of the primary hydroxy group, followed by azidation of the resultant monotosylate afforded a hydroxy azide, which was protected with TBSCl to give 10 . After 10 was hydrolyzed with NaOH, the resultant acid was converted into the corresponding activated ester,11 which when coupled with the amine 8 b , to provide amide 11 a in 96 % yield.…”

Synthesis of γ‐Aminobutyric Acid Analogs

“…A number of syntheses of enantiomerically pure GABOB (6) and carnitine (7) from malic acid (236) have been reported [171][172][173][174]. These include a seven-step synthesis via a cyclic anhydride [171], and a 13-step [172] and later six-step synthesis [173] via an oxazolidin-2-one.…”

“…Conversion to the dibenzyl ester (237) and chemoselective reduction of the a-hydroxyester group yielded a diol, which was converted to the monotosylate (238). Substitution with trimethylamine gave a carnitine derivative that was deprotected to afford the corresponding isomer of carnitine (7) in good overall yield [174].…”

Stereoselective synthesis of γ-amino acids

“…(S)-Carnitine 22 was obtained in an identical manner using (S)-malic acid as starting material. 217 Chemoselective reduction of (R)-malic acid dimethyl ester 558 with BH 3 AEDMS complex in the presence of NaBH 4 gave diol (R)-559 in 90% yield, which by treatment with p-toluenesulfonyl chloride produced the monotosylate derivative (R)-560 in 64% yield. Nucleophilic displacement of the tosyl group in (R)-560 with sodium azide afforded the corresponding azide (R)-561 in 83% yield, which by catalytic hydrogenation in the presence of (Boc) 2 O gave the diprotected (R)-GABOB 509a in 87% yield (Scheme 146).…”