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.
Cotterill
Ian C
IC
AMRI, 21 Corporate Circle, PO Box 15098, Albany, New York 12212-5098, USA. ian.cotterill@amriglobal.com
Rich
Joseph O
JO
Scholten
Marc D
MD
Mozhaeva
Lyudmila
L
Michels
Peter C
PC
D000215:Acylation; D000903:Antibiotics, Antineoplastic / Q000096:biosynthesis* / Q000138:chemical synthesis*; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000138:chemical synthesis*; D004951:Esterification; D008049:Lipase / Q000378:metabolism*; D015394:Molecular Structure; D013237:Stereoisomerism
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D008049:Lipase