Benzyl carbamates peptide synthesis

Amino Acids. Chloroformates play a most important role for the protection of the amino group of amino acids (qv) during peptide synthesis (32). The protective carbamate formed by the reaction of benzyl chloroformate and amino acid (33) can be cleaved by hydrogenolysis to free the amine after the carboxyl group has reacted further. The selectivity of the amino groups toward chloroformates results in amino-protected amino acids with the other reactive groups unprotected (34,35). Methods for the preparation of protected amino acids on an industrial scale have been developed (36,37). A wide variety of chloroformates have been used that give various carbamates that are stable or cleaved under different conditions. 

H2/Pd-C, EtOH, 20°. < -Bromobenzyl carbonates have been developed for use in solid-phase peptide synthesis. An aryl o-bromobenzyl carbonate is stable to acidic cleavage (CF3CO2H) of a /-butyl carbamate a benzyl carbonate is cleaved. 

Notes An important functional group for protecting amines as carbamates and alcohols as benzyl carbonates. Notable for the protection of amino acids during peptide synthesis. 

Benzyl carbamate protection (Cbz or Z group see Table 10.15) was initially chosen by Merrifield for solid-phase peptide synthesis [255], The strongly acidic conditions required for its solvolysis (30% HBr in AcOH, 25 °C, 5 h) demanded the use of an acid-resistant nitrobenzyl alcohol linker. Z-protection of the a-amino group in solid-phase peptide synthesis was, however, quickly abandoned and replaced by the more acid-labile Boc protection. Benzyl carbamates can be cleaved by strongly ionizing... 

The dithiasuccinyl protection group was developed by Barany and Merrifield for use in peptide synthesis, though nowadays, it is more often deployed in ami-noglycoside and glycopeptide synthesis,2 -30 In peptide synthesis, the Dts group survives the strongly acidic conditions required to cleave fe/7-butyl and benzyl esters and carbamates. 

The synthesis of phosphinic peptides by a reverse sequence of P-C bond formation events (N+PC approach) is a less frequently applied strategy which may offer important diversification possibilities. In particular, an amidoalkylation condensation reaction between amides, aldehydes, and alkylphosphinic acids (the three-component Kabachnik-Fields reaction) affords in a single step the main pseudopeptidic backbone, thus facilitating fast screening of the nature of Pi position. In 1996, Chen and Coward observed that a mixture of benzyl carbamates, aldehydes, and alkylphosphinic acid 23 in AcCl can lead to Cbz-protected phosphinic pseudodipeptides 24 (Scheme 10a) [53]. This method was adjusted by Matziari et al. to the synthesis of Fmoc-protected phosphinic building blocks 25 and peptides thereof (Scheme 10b) [54]. 

The first step in peptide synthesis is blocking (protection) of the amine functional group of an amino acid (a compound that contains both amine and carboxylic acid functional groups). Such a reaction is shown in Section 24.7C in the reaction between Ala (alanine) and benzyl chloroformate. The functional group formed in the structure labeled Z-Ala is called a carbamate (or urethane). 

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