Synthesis (Stuttg), 2011, 1555-1560

A chemo-enzymatic synthesis of β-D-arabinofuranosyl purine nucleosides

A chemo-enzymatic synthesis of 9-(β-D-arabinofuranosyl)-2- fluoroadenine (Fludarabine) and 9-(β-D-arabinofuranosyl)-2-amino-6- methoxypurine (Nelarabine) using α-D-arabinofuranose 1-phosphate as a universal substrate and recombinant E. coli purine nucleoside phosphorylase (PNP) as a biocatalyst is described. MacDonalds method was employed for the synthesis of β-D-arabinofuranose 1-phosphate, which was prepared as a mixture with β-D-arabinopyranose 1-phosphate, starting from peracyl derivatives of D-arabinose of different isomeric (anomeric) composition. It was found that the mixed phosphates can be successfully used in the reaction with purine base catalyzed by PNP pointing to the inertia of β-D-arabinopyranose 1-phosphate in regard to PNP. Reaction of 2-fluoroadenine and -D-arabinofuranose 1-phosphate is shifted towards the formation of Fludarabine, whereas the reaction of 2-amino-6-methoxypurine reached equilibrium at a ca. equimolar ratio of the base and Nelarabine. Recombinant E. coli uridine phosphorylase catalyzed the synthesis of 1-(β-D-arabinofuranosyl)thymine (ara-T) from thymine and α-D-arabinofuranose 1-phosphate. © Georg Thieme Verlag Stuttgart · New York.

Konstantinova ID, Antonov KV, Fateev IV, Miroshnikov AI, Stepchenko VA, Baranovsky AV, Mikhailopulo IA

IBCH: 117
Ссылка на статью в журнале: http://www.thieme-connect.de/DOI/DOI?10.1055/s-0030-1260010
Кол-во цитирований на 03.2024: 24
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