Stereoselective synthesis of conformationally constrained 2'-deoxy-4'-thia beta-anomeric spirocyclic nucleosides featuring either hydroxyl configuration at C5'.
An enantioselective approach to 2'-deoxy-4'-thia spirocyclic nucleosides featuring an alpha- or beta-hydroxyl substituent at C-5' of the carbocyclic ring is detailed. The starting point is the mandelate acetal 8. The overall strategy involves the stereocontrolled dihydroxylation of this dihydrothiophene, subsequent generation of the keto acetonide 12 followed by its Meerwein-Ponndorf-Verley reduction and beta-elimination, protection of the resulting dihydroxy thiaglycal, electrophilic glycosidation according to the Haraguchi protocol, reductive removal of the phenylseleno group, and end-game global deprotection. Acquisition of the alpha- and beta-5'-isomers is equally facile. Various 1D and 2D NMR techniques are used for assigning configuration.
Dong
Shuzhi
S
Evans Chemical Laboratories, The Ohio State University, Columbus, Ohio 43210, USA.
Paquette
Leo A
LA
D008956:Models, Chemical; D008968:Molecular Conformation; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D010084:Oxidation-Reduction; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D009705:Nucleosides; D013141:Spiro Compounds