title: Enzymic acylation of 506U78 (2-amino-9-beta-D-arabinofuranosyl-6- methoxy-9H-purine), a powerful new anti-leukaemic agent.
abstract: A practical enzymic approach for acylation of 506U78 (2-amino-9-beta-D-arabinofuranosyl-6-methoxy -9H-purine), a powerful anti-leukaemic agent, is described. Novozyme-435, an immobilized preparation of Candida antarctica lipase, was used to acylate 506U78 regioselectively at the 5'-position. This rendered the compound more soluble and bioavailable. Vinyl acetate was used as the acyl donor and reactions were carried out in anhydrous 1,4-dioxane with up to 100 g/l of substrate input. Bioconversions were optimised to achieve impurity (3'-mono- and di-acetates) levels of less than 0.5%.
authors.affiliation: Bioprocessing Unit, Glaxo Wellcome Research and Development, Medicines Research Centre, Gunnels Wood Road, Stevenage, Herts., SG1 2NY, U.K.
authors.forename: M
authors.initials: M
authors.lastname: Mahmoudian
authors.forename: J
authors.initials: J
authors.lastname: Eaddy
authors.forename: M
authors.initials: M
authors.lastname: Dawson
mesh_terms: D000215:Acylation; D000970:Antineoplastic Agents / Q000737:chemistry*; D001087:Arabinonucleosides / Q000737:chemistry*; D001682:Biological Availability; D002175:Candida / Q000201:enzymology; D004800:Enzymes, Immobilized / Q000737:chemistry; D005021:Ethylamines; D005656:Fungal Proteins; D008049:Lipase / Q000737:chemistry; D015394:Molecular Structure; D012995:Solubility; D012997:Solvents; D013237:Stereoisomerism; D014753:Vinyl Compounds / Q000737:chemistry; D014867:Water
chemical_list: D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D004800:Enzymes, Immobilized; D005021:Ethylamines; D005656:Fungal Proteins; D012997:Solvents; D014753:Vinyl Compounds; D014867:Water; C104457:nelarabine; C093667:Novozyme 435; D008049:Lipase; C011566:vinyl acetate; C016162:triethylamine