• Bulletin of the Korean Chemical Society
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• v.32 no.1
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• pp.315-318
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• 2011

• Applied Chemistry for Engineering
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• v.26 no.1
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• pp.111-115
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• 2015

Two new analogs of bestatin were prepared from $\small{D}$-leucine and $\small{D}$-valine in a stereoselective and efficient way. An aminopeptidase inhibitor bestatin shows significant biological effects on immunomodulation and is marketed for the treatment of acute myelocytic leukemia. The key intermediates, trans-oxazolidine methyl esters 2a and 2b, were obtained with more than 20 to 1 stereoselectivity in a one-pot procedure by the three cascade reactions between N-hydroxymethyl protected ${\alpha}$-amino aldehydes (4a and 4b) and phenylsulfonylnitromethane ($PhSO_2CH_2NO_2$) and the following in-situ ozonolysis. Basic hydrolysis of 2a and 2b, and then the peptide coupling with $\small{L}$-Leu-OMe produced the protected derivatives of two new bestatin analogs, 3a and 3b, respectively. The new isobutyl and isopropyl analogs of bestatin (1a and 1b) were produced in overall 51% and 38% yields, respectively, with high stereoselectivity from the corresponding protected ${\alpha}$-amino aldehydes 4 in a six-step process.