Ozonolysis peptide coupling

A solid-phase technique that uses an N-protected u,p-unsaturated y-amino acid proved to be effective for ozonolysis due to its ethylenic functionality. The linker was prepared from the Wittig reaction between (ethoxycarbonylethylene)triphenylphosphorane and either the Boc or Fmoc N-protected a-amino aldehyde. The Boc or Fmoc protecting group was removed and the chain was elongated by standard BOP coupling 49,52 53 61 The peptide-resin was then cleaved by ozonolysis, which afforded the desired aldehyde 49 ... 

The starting substrate, protected ot-vinylproline 187 was activated by HATU and coupled with glycine methyl ester hydrochloride to give protected peptide derivatives 188. Further, ozonolysis of these derivatives and subsequent reduction with excess of Na[BH(OAc)3] provided the hydroxymethyl-substituted derivative 189 in... 

It was shown <1999BML3255> that a crystalline ozonide obtained by ozonolysis of the A-allylamidc of Cbz-L-phenylalanine inhibits papain, a cysteine protease. Reduction of that ozonide in excess dimethyl sulfoxide (DMSO) generates in situ a peptide aldehyde, as proved by coupling with a stabilized Wittig ylide forming thereby an unsaturated ester. 

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