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 derivati...

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Veröffentlicht in:	Biotechnology and bioengineering 2008-10, Vol.101 (3), p.435-440
Hauptverfasser:	Cotterill, Ian C, Rich, Joseph O, Scholten, Marc D, Mozhaeva, Lyudmila, Michels, Peter C
Format:	Artikel
Sprache:	eng
Schlagworte:	Acylation Antibiotics, Antineoplastic - biosynthesis Antibiotics, Antineoplastic - chemical synthesis Biochemistry Bioconversions. Hemisynthesis Biological and medical sciences Biotechnology Catalysis Chemical synthesis Chromatography Doxorubicin - analogs & derivatives Doxorubicin - biosynthesis Doxorubicin - chemical synthesis doxorubicin esterification enzymatic synthesis Enzymes Esterification Fundamental and applied biological sciences. Psychology Lipase - metabolism Methods. Procedures. Technologies Molecular Structure reversible derivatization Salt Stereoisomerism
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Beschreibung
Zusammenfassung:	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.
ISSN:	0006-3592 1097-0290
DOI:	10.1002/bit.21929