SPOS of Olefin-Containing Peptides Using the Horner-Emmons Reaction

Significance

The syntheses of olefin-containing peptides by the solid-phase Horner-Emmons reaction were demonstrated. Thus, for example, the resin-supported peptide 2 prepared from cross-linked ethoxylate acrylate resin (CLEAR)-supported Fmoc-Glu-O-allyl (1) was treated with Dess-Martin periodinane followed by the Horner-Emmons reaction with allyl diethylphosphonoacetate/[Me₃Si]₂NLi to give (E)-olefin peptide 3. After cleavage of the allyl ester with Pd(PPh₃)₄, H-Pro-O-allyl was coupled with 3 using HATU/HOAt to give peptide 4. Removal of the protecting groups followed by cleavage from resin by TFA/H₂O (95:5) afforded the desired (E)-olefin peptide 5 in 20% yield. For CLEAR support, see: M. Kempe, G. Barany J. Am. Chem. Soc. 1996, 118, 7083-7093.