M. Ikunaka, J. Matsumoto, Yukifumi Nishimoto
Jun 21, 2002
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Journal
Tetrahedron-asymmetry
Abstract
Abstract Scalable syntheses of (2 S ,3 S )-3- N - tert -butoxycarbonylamino-2-hydroxy-4-phenylbutanoic acid (BocAHPBA) 1 and ( R )-3- tert -butoxycarbonyl-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid (BocDMTA) 2 have been developed. Both 1 and 2 can serve as chiral building blocks in assembling JE-2147 (KNI-764) 3 , a potent HIV protease inhibitor. The synthesis of (2 S ,3 S )-BocAHPBA 1 is achieved in 41% overall yield from ( S )-2- N , N -dibenzylamino-3-phenylpropanal 4 in five steps where Tamao's reagent [Me 2 ( i -PrO)SiCH 2 MgCl] is employed for a one-carbon homologation, and Zhao's oxidation protocol (TEMPO, NaClO 2 , NaClO) is applied to convert a 1,2-glycol moiety into an α-hydroxy acid motif. ( R )-BocDMTA 2 is synthesized with 99.4% ee in 24% yield via enantioselective hydrolysis of methyl (±)-5,5-dimethyl-1,3-thiazolidine-4-carboxylate 8b by a Klebsiella oxytoca hydrolase; the unreacted ( S )-ester 8b can be recovered and racemized with NaOMe to afford (±)- 8b in 46% yield for another round of the enzymatic processing.