Boc-DL-β-Phe-OH

C17H25NO4S, Mr = 339.5, monoclonic, C2 a = 24.927 (8), b = 5.252 (4), c = 16.867 (7) A, beta = 122.70 (1) degree, V = 1858.2 (9) A3, Z = 4, D chi = 1.21 g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 1.83 cm-1, F(000) = 728, T = 295 K. The final R value for 1466 independent observed reflections is 0.075. The thiomethylene dipeptide analogue possesses a C alpha i...C alpha i+1 distance somewhat smaller than in the extended amide counterpart due to a partially folded structure, especially in the C-terminal region. Pairs of molecules are held together by O-H...O = C (carboxylic acid) hydrogen bonds.

Approaches to the synthesis of model compounds based on the tylosin-related macrolides desmycosin and O-mycaminosyltylonolide were developed using specially designed peptide derivatives of macrolide antibiotics to study the conformation and topography of the nascent peptide chain in the ribosome tunnel. A method for selective bromoacetylation of desmycosin at the hydroxyl group of mycinose was developed, which involves preliminary acetylation of mycaminose. The reaction of the 4"-bromoacetyl derivative of the antibiotic with cesium salts of the dipeptide Boc-Ala-Ala-OH and the hexapeptide MeOTr-Gly-Pro-Gly-Pro-Gly-Pro-OH led to the corresponding peptide derivatives of desmycosin. The protected peptides Boc-Ala-Ala-OH, Boc-Ala-Ala-Phe-OH, and Boc-Gly-Pro-Gly-Pro-Gly-Pro-OH were condensed with the C23-hydroxyl group of O-mycaminosyltylonolide.

4-Dimethylaminopyridine (DMAP) was found to be useful in the enhancement of peptide coupling reactions mediated by dicyclohexylcarbodiimide or symmetrical anhydrides. In an automated synthesis of the model heptapeptide Boc-Ala-Cle-Ile-Val-Pro-Arg(Tos)-Gly-OCH2-Resin (Cle, cycloleucine), the efficiencies of various coupling methods such as dicyclohexylcarbodiimide, dicyclohexylcarbodiimide plus 1-hydroxybenzotriazole, and symmetrical anhydride were compared with that of dicyclohexylcarbodiimide plus 4-dimethylaminopyridine. Based on the amino acid composition of the peptide-resin samples and high pressure liquid chromatographic analyses of the protected heptapeptide amide obtained from the ammonolytic cleavage of the peptide-resin samples, it was concluded that only dicyclohexylcarbodiimide plus 4-dimethylaminopyridine gave the desired near quantitative couplings in those cycles involving the sterically hindered amino acid residues. Observations were also made that 4-dimethylaminopyridine was a useful additive in a modified symmetrical anhydride method of coupling.

In the synthesis of the double-chain bis-cystinyl hinge fragment 225-232/225'-232' of the human IgG1, which contains two N-terminal threonine residues, the final acidolytic deprotection step, with 99% aqueous trifluoroacetic acid, was accompanied by formation of remarkable amounts of an unknown side product. This has been identified as the N alpha-mono-trifluoroacetylated product; however, even bis-trifluoroacetylation was found to occur by prolonged exposure of the parallel dimer to the reaction medium. Similarly, the model compounds H-Thr(tBu)-Phe-OH, [Boc-Thr(tBu)-Cys-OH]2 and Boc-Thr(tBu)-Cys(StBu)-Ala-OH were acylated by treatment with trifluoroacetic acid at rates that suggest a rather pronounced sequence dependency. Since, on the other hand, the model compound [Boc-Ala-Cys-OH]2 was not trifluoroacetylated at all under identical conditions, the reaction has to proceed prevalently via intermediate formation of the trifluoroacetyl ester of N-terminal hydroxyamino acids, followed by O-->N shift according to the hydroxyoxazolidine mechanism.