title: Radiosynthesis of [14C]acarbose.
abstract: Acarbose (O-4,6-dideoxy-4-[[(1S, 4R, 5S, 6S)-4,5,6-trihydroxy-3- (hydroxymethyl)-2-cyclohexen-1-yl]amino]-a-D-glucopyranosyl-(1---- 4)-O-a-D- glucopyranosyl-(1----4)-4-glucopyranose, Bay g 5421), an a-glucosidase inhibitor from Actinoplanes, has been developed for the treatment of diabetes mellitus. To investigate the pharmacokinetics and the biotransformation, 14C-labelled acarbose ([14C]Bay g 5421) was required. About 37 GBq (1 Ci) D-[U-14C]glucose was used as a precursor to obtain [14C]acarbose with a radiochemical yield of between 1.58 and 2.56%. For fermentation purposes resting cells of the Actinoplanes mutant SN 1667/47 were used under cometabolism conditions with a 10-fold excess of maltose. The specific radioactivities achieved in individual preparations were 7.77 MBq/mg (210 microCi/mg), 8.03 MBq/mg (217 microCi/mg), and 9.14 MBq/mg (247 microCi/mg), with a radiochemical purity of greater than 98% in each case. By hydrolysis and subsequent investigation of the hydrolysis products it was shown that [14C]carbon atoms originating from the radioactive glucose are present only in the core and not in the maltose unit of [14C]acarbose.
authors.affiliation: Pharma Research Center, Bayer AG, Wuppertal, Fed. Rep. of Germany.
authors.forename: W
authors.initials: W
authors.lastname: Maul
authors.forename: L
authors.initials: L
authors.lastname: Müller
authors.forename: J
authors.initials: J
authors.lastname: Pfitzner
authors.forename: E
authors.initials: E
authors.lastname: Rauenbusch
authors.forename: H
authors.initials: H
authors.lastname: Schutt
mesh_terms: D020909:Acarbose; D000192:Actinomycetales / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D003470:Culture Media; D005285:Fermentation; D006868:Hydrolysis; D007553:Isotope Labeling; D011854:Radiochemistry; D013393:Sucrase / Q000037:antagonists & inhibitors; D014312:Trisaccharides / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D003470:Culture Media; D014312:Trisaccharides; D013393:Sucrase; D020909:Acarbose