Further metabolic studies of indole and sugar derivatives using the staurosporine producer Streptomyces staurosporeus.
During our continuing studies of staurosporine (1) biosynthesis and the metabolism of indole derivatives, three additional novel metabolites, beta-hydroxy-Nb-acetyltryptamine (7) and its 5- and 6-fluoro derivatives (8 and 9, respectively), were isolated, respectively, from the feeding of tryptamine and 5- and 6-fluorotryptamines using Streptomyces staurosporeus. In addition, two new 5-hydroxytryptamine (serotonin) metabolites, Nb-acetyltryptamine-5-O-beta-D-quinovopyranoside (11) and Nb-acetyltryptamine-5-O-alpha-L-rhamnopyranoside (12), were isolated along with 5-hydroxy-Nb-acetyltryptamine (10). From a glucose containing medium, 6-O-acetylglucose and its 13C uniformly labeled derivative were isolated from a culture of S. staurosporeus during biosynthetic studies of 1. In 2-deoxyglucose metabolism studies, 6-O-acetyl-2-deoxyglucose was isolated and identified as a metabolic product of 2-deoxyglucose. A copper-enzyme inhibitor, N,N-diethyldithiocarbamic acid, was evaluated for the accumulation of staurosporine intermediates; however, no modified staurosporines were observed.
Yang
S W
SW
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago 00612, USA.
Cordell
G A
GA
D000963:Antimetabolites / Q000494:pharmacology; D050260:Carbohydrate Metabolism; D002240:Carbohydrate Sequence; D002241:Carbohydrates / Q000737:chemistry; D002855:Chromatography, Thin Layer; D003470:Culture Media; D003847:Deoxyglucose / Q000494:pharmacology; D004050:Ditiocarb / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005285:Fermentation; D007211:Indoles / Q000737:chemistry / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D019311:Staurosporine / Q000096:biosynthesis* / Q000737:chemistry; D013302:Streptomyces / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*
D000963:Antimetabolites; D002241:Carbohydrates; D003470:Culture Media; D004791:Enzyme Inhibitors; D007211:Indoles; D004050:Ditiocarb; D003847:Deoxyglucose; D019311:Staurosporine