Serine-cis-proline and serine-trans-proline isosteres: stereoselective synthesis of (Z)- and (E)-alkene mimics by Still-Wittig and Ireland-Claisen rearrangements.
Two new amide isosteres of Ser-cis-Pro and Ser-trans-Pro dipeptides were designed and stereoselectively synthesized to be incorporated into potential inhibitors of the phosphorylation-dependent peptidylprolyl isomerase Pin1, an essential regulator of the cell cycle. The cis mimic, the (Z)-alkene isomer, was formed through the use of a Still-Wittig [2,3]-sigmatropic rearrangement, while the trans mimic, the (E)-alkene, was synthesized through the use of an Ireland-Claisen [3,3]-sigmatropic rearrangement. Starting from N-Boc-Ser(OBn)-N(OMe)Me, both mimics were synthesized in Boc-protected form suitable for peptide synthesis with an overall yield of 20% in 10 steps for the cis mimic and 13% in eight steps for the trans mimic.
Wang
Xiaodong J
XJ
Department of Chemistry, MC 0212, Virginia Tech, Blacksburg, Virginia 24061, USA.
Hart
Scott A
SA
Xu
Bailing
B
Mason
Matthew D
MD
Goodell
John R
JR
Etzkorn
Felicia A
FA
D000475:Alkenes / Q000737:chemistry*; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods; D004151:Dipeptides / Q000032:analysis / Q000138:chemical synthesis*; D018716:Molecular Mimicry; D015394:Molecular Structure; D011392:Proline / Q000737:chemistry*; D012694:Serine / Q000737:chemistry*; D013237:Stereoisomerism
D000475:Alkenes; D004151:Dipeptides; C465983:seryl-proline; D012694:Serine; D011392:Proline