New Reactions of the Thiocarbonyl Function. The Synthesis of Hindered Peptides

ABSTRACT:

The well-known radical chemistry of the thiocarbonyl function has been expanded to include the concerted reaction between an O-acyl derivative of N-hydroxypyridine-2(1H)-thione (a Barton PTOC ester) and a sulfenamide. The atom-economical process spawned a carboxamide and an unsymmetrical disulfide of synthetic and biological value. The reaction was successfully applied to the synthesis of sterically encumbered, urethane-protected dipeptides. The oxidation-reduction technology pertaining to the disulfide-phosphine combination facilitated the generation of transient Barton PTOC esters, In conjunction with the appropriate benzenesulfenamide, the Barton PTOC ester of benzoyl-L-leucine was shown to preserve optical integrity according to the sensitive Young test, albeit at low temperature. However, the thermodynamic forces at play are powerful and, as a result, the yields were not compromised. In all but the sterically demanding instances, the parent free amine almost matched the reaction time, yield, and enantiomeric excess of the corresponding benzenesulfenamide in its reaction with a Barton PTOC ester.

KEY WORDS::

• Barton PTOC esters
• sulfenamides
• concerted mechanism
• steric hindrance
• oxidation-reduction condensation
• optical integrity