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A Facile Synthesis of 1,5‐Disubstituted Tetrazole Peptidomimetics by Desulfurization/Electrocyclization of Thiopeptides
Author(s) -
Prabhu Girish,
Nagendra Govindappa,
Sagar N. R.,
Pal Rumpa,
Guru Row Tayur N.,
Sureshbabu Vommina V.
Publication year - 2016
Publication title -
asian journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.846
H-Index - 44
eISSN - 2193-5815
pISSN - 2193-5807
DOI - 10.1002/ajoc.201500384
Subject(s) - tetrazole , chemistry , peptidomimetic , hypervalent molecule , isostere , reagent , amide , combinatorial chemistry , stereochemistry , peptide , organic chemistry , biochemistry
Abstract The cis ‐amide bond isostere, 1,5‐disubstituted tetrazole,has been introduced in the peptide backbone by a simple route starting from the thiopeptide. The desired 1,5‐disubstituted tetrazole peptidomimetics were synthesized by the desulfurization of thiopeptides by using HgCl 2 in the presence of NaN 3 /TEA in DMF in good yields. Various other thiophilic reagents including hypervalent iodine reagents failed to deliver the tetrazole product with the exception of CBr 4 /PPh 3 , which resulted in moderate yields. The advantage of the present protocol over previous methods has been demonstrated by the selective insertion of tetrazole into peptide–thiopeptide hybrids. Also, the protocol is compatible with commonly employed urethane protecting groups (Fmoc, Boc, and Cbz) in peptide chemistry. Thiopeptide Boc‐Pro‐ψ[CSNH]‐Val‐OMe ( 2 i ) and two tetrazole peptidomimetics Cbz‐Ala‐ψ[CN 4 ]‐Phe‐OMe ( 3 d ) and Boc‐Pro‐ψ[CN 4 ]‐Val‐OMe ( 3 i ) were obtained as single crystals and their molecular structures have been confirmed by X‐ray crystallography.