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Reversible derivatization to enhance enzymatic synthesis: Chemoenzymatic synthesis of doxorubicin-14-O-esters

✍ Scribed by Ian C. Cotterill; Joseph O. Rich; Marc D. Scholten; Lyudmila Mozhaeva; Peter C. Michels


Publisher
John Wiley and Sons
Year
2008
Tongue
English
Weight
122 KB
Volume
101
Category
Article
ISSN
0006-3592

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✦ Synopsis


Abstract

An efficient three‐step, chemoenzymatic synthesis of unprotected doxorubicin‐14‐O‐esters from doxorubicin hydrochloride salt is described. The key step is a lipase‐catalyzed regioselective transesterification/esterification using commercially available acyl donors and doxorubicin reversibly derivatized with N‐alloc to improve substrate loadings. The overall yield is ca. 60% and chromatographic purification is not required, thereby making the process more amenable to scale‐up. Biotechnol. Bioeng. 2008;101: 435–440. © 2008 Wiley Periodicals, Inc.