Stereoselective synthesis of beta-anomeric 4'-thiaspirocyclic ribonucleosides carrying the full complement of RNA-level hydroxyl substitution.
[reaction: see text] Stereoselective syntheses of a group of 4'-thiaspirocyclic ribonucleosides featuring both pyrimidine and purine classes and both possible configurations at C-5' are described. Use is made of the Pummerer reaction of substrates carrying an alpha-oriented 2,4-dimethoxybenzoyloxy substituent at C-2 in order to gain reliable stereocontrol via neighboring group participation. Irrespective of the S or R configuration of the pivotal sulfoxide intermediates, the nucleobase is captured from the beta-face. The competing process is formation of unsaturated sulfoxides, presumably via competing E2-type elimination. Although differences in reactivity between the two stereoisomeric series were noted, the common route has successfully given rise for the first time to desirable beta-anomeric sulfur-containing spiroribonucleosides with minimum formation of the alpha-anomers.
Evans Chemical Laboratories, The Ohio State University, Columbus, Ohio 43210, USA. paquette.1@osu.edu
Leo A
LA
Paquette
Shuzhi
S
Dong
D003500:Cyclization; D008956:Models, Chemical; D012313:RNA / Q000737:chemistry*; D012263:Ribonucleosides / Q000138:chemical synthesis*; D013141:Spiro Compounds / Q000138:chemical synthesis*; D013237:Stereoisomerism; D013454:Sulfoxides / Q000737:chemistry
D012263:Ribonucleosides; D013141:Spiro Compounds; D013454:Sulfoxides; D012313:RNA