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http://dx.doi.org/10.14478/ace.2014.1134

Stereoselective Synthesis of Novel Bestatin Analogs  

Seo, Youngran (Department of Chemical and Biological Engineering, Seoul National University)
Lee, SooBeom (Department of Chemical and Biological Engineering, Seoul National University)
Kim, Young Gyu (Department of Chemical and Biological Engineering, Seoul National University)
Publication Information
Applied Chemistry for Engineering / v.26, no.1, 2015 , pp. 111-115 More about this Journal
Abstract
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.
Keywords
bestatin analogs; aminopeptidase inhibitor; ${\beta}$-amino-${\alpha}$-hydroxy acid; intramolecular conjugate addition;
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