SYNTHESIS OF NEW ANTHRACYCLINE DERIVATIVES CONTAINING PYRUVIC, ASPARTIC, ORN-ACETYLASPARTIC ACID MOLECULE

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

“…The literature on doxorubicin structure-activity relationships provides some direction for focusing analog design. In particular, the synthesis of doxorubicin C-14 ester derivatives and their evaluation as anti-cancer agents has been widely studied (Arcamone et al, 1974;Ghirmai et al, 2005;Rho et al, 2002). Indeed, the 14-O-valerate of doxorubicin-3 0 -trifluoroacetamide (Valrubicin, 10) has found clinical use with improved toxicity over doxorubicin in the treatment of certain bladder cancers (Kuznetsov et al, 2001;Newling et al, 2001;Onrust and Lamb, 1999).…”

“…The accepted chemical synthetic route to C-14 ester derivatives entails the nucleophilic displacement-type esterification of 14-bromodaunorubicin HCl 2 (prepared by bromination of 3) with the salt of the appropriate acid (Arcamone et al, 1974;Ghirmai et al, 2005;Rho et al, 2002). While overall yields are acceptable (40-50%), the removal of the resulting aglycone by-product requires chromatographic separation.…”