Creation of Nonplanar Thioamide and Conformation Analysis of Oligothiopeptides Based on 7-Azabicyclo[2.2.1]heptane

Abstract

While thioamides show a strong preference for planar structures, little has been reported about their deviation from planarity. Our X-ray crystallographic analysis showed that N-thioaroyl-7-azabicyclo[2.2.1]heptane displays substantial nonplanarity (1a: alpha = 167.3 deg. and |tau| = 11.0 deg.) as compared with monocyclic pyrrolidine thioamide (2a: alpha = 174.7 deg. and |tau| = 3.9 deg.). A reduced rotational barrier, that is, reduced enthalpy of activation for thioamide rotation of 1a as compared with that of 2a in nitrobenzene-d₅, is consistent with the postulate that 1a takes a nonplanar thioamide structure in solution. Furthermore, synthesis and solution structure of beta-thiopeptides based on the 7-azabicyclo[2.2.1]heptane skeleton will be discussed.