Pentachlorophenyl esters carbonates

In solution-phase peptide synthesis, acylation of amino acids or peptides with N-protected azetidine-2-carboxylic acid is performed via the active esters, e.g. A-hydroxysuccin-imide 100 111-112 or pentachlorophenyl ester, m 117 as well as by the mixed anhydride 101114 or carbodiimide 118 methods. An attempt to prepare the A-carbonic acid anhydride by cycli-zation of A-(chloroformyl)azetidine-2-carboxylic acid with silver oxide in acetone or by addition of triethylamine in situ failed, presumably due to steric hindrance. 111 In SPPS, activation of the Fmoc-protected imino acid by HBTU 119,120 is reported. In solution-phase peptide synthesis, coupling of N-protected amino acids or peptides to C-protected azetidine-2-carboxylic acid or related peptides may be performed by active esters, 100 118 121 mixed anhydrides, 95 or similar methods. It may be worth mentioning that the probability of pip-erazine-2,5-dione formation from azetidine-2-carboxylic acid dipeptides is significantly reduced compared to proline dipeptides. 111 ... 

Carbonic acid, tert-butyl pentachlorophenyl ester (8) Carbonic acid,... 

In the discussion of side reactions we have dealt, so far, only with electronic effects. It would be a mistake, however, to underestimate the importance of geometric factors and, in particular, the influence of bulky side chains. Branching of the aliphatic chain in valine and in isoleucine is at the jS-carbon atom, near to the reactive carbonyl group in activated intermediates. Hence, acylation reactions in which these amino acids are involved, do not proceed at a rate observed with other amino acids, for instance with leucine, in which branching is at the y-carbon atom. Steric hindrance becomes even more pronounced when the activating group is similarly bulky as in pentachlorophenyl esters ... 

Mixed carbonic anhydride N-Carboxyanhydride N-Thiocarboxyamino acid anhydride Benzhydroxamic acid ester Cyanomethyl ester 8-Hydroxyquinoline ester p-Nitrophenyl ester Phenylazophenyl ester Pentachlorophenyl ester Pentafluorophenyl ester Phenyl ester... 

Peptide synthesis, N-protection Acetic-formic anhydride. Adamantyl chloroformate. Benzylthiocarbonyl chloride. /-Butoxycarbonyl-N-hydroxysuccinimide ester. /-Butyl azido-formate. /-Butylcarbonic diethylphosphoric anhydride. /-Butyl fluoroformate. /-Butyl oxycarbonyl fluoride. /-Butyl pentachlorophenyl carbonate. /-Butyl 2,4,5-trichlorophenyl carbonate. Carbobenzoxy chloride. 3,5-Dimethoxybenzyl p-nitrophenyl carbonate. [2-(Diphenyl)isopropyljphenyl carbonate. /-Pentyl chloroformate. 

One-step proeess. A soln. of benzyl p-nitrophenyl carbonate in dioxane added to aq. Na-glycinate (prepared from glycine and NaHGOg) heated 3 hrs. at 100°, 1 N HGl added in the cold followed by a soln. of dicyclohexylcarbodiimide in dioxane, kept 0.5 hr. in an ice-bath, and 2 hrs. at room temp. benzyloxy-carbonylglycine p-nitrophenyl ester. Y 78%. F. e. s. Y. Wolman, D. Ladkany, and M. Frankel, Soc. (G) 1967, 689 with ferf-butyl 2,4,5-trichlorophenyl carbonate, co-extraction of the intermediates, cf. W. Broadbent, J. S. Morley, and B. E. Stone, Soc. (G) 1967, 2632 with ferf-butyl pentachlorophenyl carbonate cf. M. Fujino and G. Hatanaka, Ghem. Pharm. Bull. 15, 2015 (1967). 

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