Studies of N-Terminal Templates for α-Helix Formation. Synthesis and Conformational Analysis of (2S,5S,8S,11S)-1-Acetyl-1,4-diaza-3-keto-5-carboxy-10-thiatricyclo4,8>tridecane (Ac-Hel1-OH)

Article abstract of DOI:10.1021/jo00023a037

A convergent synthesis of the title compound, a conformationally restricted analogue of acetyl-L-prolyl-L-proline, from 1-acetyl-2(S)-carboxy-4(S)-mercaptopyrrolidine and trans-1-(tert-butoxycarbonyl)-2(S)-(methoxycarbonyl)-5(S)-<(tosyloxy)methyl>pyrrolidine (Ac-Hel1-OH) is reported, along with a synthesis of (2S,8S,11S)-1-acetyl-1,4-diaza-3-keto-10-thiatricyclo<2.8.1.0^4,8>tridecane.In the crystal and in CDCl3 solution the conformation of Ac-Hel1-OH is shown to approximate a staggered orientation at the 8,9-CC bond and an s-cis orientation at the acetyl amide bond.In DMF, DMSO, MeCN, and D2O significant amounts of the s-trans conformer are also present.