Peptide Synthesis with Benzo- and Naphthosultones

Article abstract of DOI:10.1021/jo00196a006

6-Nitro- and 6,8-dinitronaphth<1,8-cd>-1,2-oxathiole S,S-dioxides (7b and 7c) have been prepared from the parent naphthosultone 7a and compared with 5-nitrobenz<1,6-d>-3H-1,2-oxathiole S,S-dioxide (1b) as coupling reagents for peptide synthesis.Nucleophilic attack of a carboxylate salt on these strained five-membered sultones leads to activated esters 3 and 9 which rapidly react with amines (except in the case of 9c).The rate constant for the formation of ester 9b is higher than that of 3b.Amides or peptides are formed in slightly better yields with the naphthosultone 7b than with the benzosultone 1b.The naphthosultones are also preferred over the benzosultones from the point of view of amount of 5(4H)-oxazolone formation from N-benzoyl amino acids and the degree of racemization.However the rate of alkaline hydrolysis of 7b is slower than that of 1b.All these results may be rationalized by a better intramolecular acyl transfer reaction in the more rigid mixed anhydride intermediate 8b.There is no dependence on in the rate equation for aminolysis of esters 3b and 9b by benzylamine in THF, acetonitrile, or DMF and the aminolysis is probably anchimerically assisted by a neighbouring S=O group.Esters 3b are more selective acylating agents for primary amino groups in the presence of secondary ones than esters 9b and this observation is exploited in a synthesis of maytenine by selective acylation of spermidine.