Synthesis of Peptides with α,β‐Dehydroamino Acids, V. Coupling experiments with C‐Terminal Dehydrophenylalanine and Dehydroalanine Residues

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Abstract
N‐Protected model dipeptides of C‐terminal (Z)‐ΔPhe and ΔAla couple with glycine esters after activation with either diphenyl phosphorazidate (DPPA), N‐cyclohexyl‐N′‐[2‐(N‐methylmorpholinio)ethyl]carbodiimide p‐toluenesulfonate (WSC), N,N′‐dicyclohexylcarbodiimide + 1‐hydroxybenzotriazole (DCC + HOBt), or the mixed anhydride (MA) with isobutyl chlorocarbonate to give in good or mostly moderate yields the (Z)‐ΔPhe‐containing tripeptides 1 – 9 and ΔAla‐containing tripeptides 11 – 19, respectively. In the MA and DPPA methods, further acylation products 20a – d are formed to a great extent, expecially during the ΔAla peptide syntheses. (E)‐TFA‐Gly‐ΔPhe and Gly‐OtBu, irrespective of the activation method, afford mixtures of (Z)‐ and (E)‐tripeptides 1 and 10 with small amounts of the (E)‐isomer 10. Addition products to the ΔAla double bond were isolated. They are azidotripeptides 21a – 1 formed if the DPPA method is used. An adduct 22 from tripeptide and HOBt arises from the WSC + HOBt method. In the MA method, loss of the ΔAla residue is observed and X‐Gly‐Gly‐OY 23a and b are obtained. The previously N‐deprotected tripeptides 1 and 11 were condensed with Boc‐Gly‐OSu to yield the tetrapeptides 24 and 25.