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

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.