title: Development of a highly beta-selective ribosylation reaction without using neighboring group participation: total synthesis of (+)-caprazol, a core structure of caprazamycins.
abstract: Full details of the total synthesis of (+)-caprazol are described. The key elements of our approach include the early stage introduction of the aminoribose in a highly beta-selective manner, using the steric hindrance in the transition state and the construction of the diazepanone by a modified intramolecular reductive amination. The 5'-C-glycyluridine derivative 9, which was prepared stereoselectively via Sharpless asymmetric aminohydroxylation, was ribosylated with 2,3-O-alkylidene ribofuranosyl donors. It was revealed that increasing the size of the alkyl substituents of the acetal unit resulted in improving the stereoselectivity of the anomeric position, and the desired ribosides 21b (1' '-beta) and 22b (1' '-alpha) were obtained in 80% yield (21b/22b = 24.0/1) when the ribosyl fluoride 16 possessing a more sterically hindered 3-pentylidene group was used. The origin of the stereoselectivity of the ribosylation was also discussed. Construction of the diazepanone system was optimized with the model aldehyde 37, and the desired diazepanone 38 was obtained in 88% yield via two-step reaction sequence including catalytic hydrogenation followed by hydride reduction. Application of this method to the aldehyde 44 successfully afforded the diazepanone derivatives 45 and 46, functional group manipulation of which completed the total synthesis of (+)-caprazol.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Shinpei
authors.initials: S
authors.lastname: Hirano
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ichikawa
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuda
mesh_terms: D000606:Amino Sugars / Q000737:chemistry*; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry*; D006031:Glycosylation; D008055:Lipids / Q000737:chemistry*; D008956:Models, Chemical; D008968:Molecular Conformation; D009705:Nucleosides / Q000737:chemistry*; D012266:Ribose / Q000031:analogs & derivatives* / Q000737:chemistry; D013237:Stereoisomerism; D014529:Uridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: C481638:1-amino-1-deoxyribose; D000606:Amino Sugars; D001381:Azepines; D008055:Lipids; D009705:Nucleosides; C512217:caprazamycin A; C476914:caprazamycin B; C512218:caprazamycin C; C512216:caprazol; D012266:Ribose; D014529:Uridine