A method for stabilizing the cis prolyl peptide bond: influence of an unusual n -%26gt; pi* interaction in 1,3-oxazine and 1,3-thiazine containing peptidomimetics

作者：Reddy Damodara N; Thirupathi Ravula; Tumminakatti Shama; Prabhakaran Erode N^*

来源：Tetrahedron Letters, 2012, 53(33): 4413-4417.

DOI：10.1016/j.tetlet.2012.06.031

• n -%26gt
• pi* Interactions
• Oxazine
• Thiazine
• cis-trans Isomerism
• cis Peptide bond

The cis/trans isomer ratios of the Xaa-Pyr (Pyr = pyrrolidine) 3 degrees amide bonds are significantly high (similar to 90% cis) in the novel peptidomimetics where Pyr contains 1,3-oxazine (Oxa) or 1,3-thiazine (Thi) at its 2 position. We find that an unusual n -%26gt; pi(i-1)* interaction, selectively stabilizes the cis conformer and the n X n repulsion destabilizes the trans conformer of these molecules. Both these electronic effects oppose the steric effects in the 3 degrees amide bond. The structural requirements for manifestation of these electronic effects are determined.

• 出版日期2012-8-15