Efficient synthesis of natural aminopeptidase inhibitors, bestatin and AHPBA-Val = Efficient synthesis of natural aminopeptidase inhibitors, bestatin and AHPBA-Val

다국어 초록 (Multilingual Abstract)

Bestatin and AHPBA-Val are known as inhibitors to aminopeptidase N (APN). The bioactivity of bestatin and AHPBA-Val is closely related to the stereochemistry of β-amino-α-hydroxy acid moiety. However, the desired stereochemistry had been mostly given by chiral catalysts or chiral auxiliaries. Contrast to the previous reagent controlled methods, the chiral synthon for (2S,3R)-3-amino-2-hydroxy-4-phenylbutanoic acid was stereoselectively prepared from the N-hydroxymethyl protected α-amino aldehyde via the intramolecular conjugate addition. The prepared synthon, trans-methoxymethyl-oxazolidine, was converted to bestatin and AHPBA-Val in 85% and 62% yields via 4 steps without separate production and deprotection steps of the vicinal amino alcohol.