title: Phenylsulfanylation of 3',4'-unsaturated adenosine employing thiophenol-N-iodosuccinimide leads to 4'-phenylsulfanylcordycepin: synthesis of 4'-substituted cordycepins on the basis of substitution of the phenylsulfanyl leaving group.
abstract: Upon reaction of the 3',4'-unsaturated adenosine derivative 2 with N-iodosuccinimide (NIS) and thiophenol, an unexpected electrophilic hydrophenylsulfanylation proceeded to provide 4'-phenylsulfanylcordycepin 7 in 79% yield with the ratio 7a/7b = 6.6/1. A study of the reaction mechanism revealed that hydrogen iodide (HI) generated from NIS and PhSH acted as an active species. On the basis of a deuterium experiment using PhSD, initial protonation occurred at the β face of the double bond to furnish the β-π complex III, which underwent anti addition of PhSH as a major pathway. Nucleophilic substitution of N(6)-pivaloylated 9 with various alcohols in the presence of N-bromosuccinimide (NBS) gave the respective 4'-α-alkoxycordycepins 15a-21a as the major stereoisomers. Use of DAST in place of an alcohol gave the 4'-α-fluoro analogue 23a stereoselectively. Radical-mediated carbon-carbon bond construction was also applicable to 7, giving 4'-α-allylcordycepin (24a) and 4'-α-cyanoethylcordycepin (25) derivatives.
authors.affiliation: School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. y-kubota@pharm.showa-u.ac.jp
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kubota
authors.forename: Mariko
authors.initials: M
authors.lastname: Ehara
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Haraguchi
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Tanaka
mesh_terms: D000241:Adenosine / Q000737:chemistry*; D003839:Deoxyadenosines / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D010636:Phenols / Q000737:chemistry; D013237:Stereoisomerism; D013388:Succinimides / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: C570465:4'-alpha-cyanoethylcordycepin; C570464:4'-phenylsulfanylcordycepin; D003839:Deoxyadenosines; D010636:Phenols; D013388:Succinimides; D013438:Sulfhydryl Compounds; C570463:thiophenol-N-iodosuccinimide; C008155:N-iodosuccinimide; C042983:thiophenol; C058120:cordycepin; D000241:Adenosine