Racemization of amino acid derivatives. III. Rate of racemization and peptide bond formation of cysteine active esters

Abstract

the layers were separated. The aqueous layer was neutralized with sodium bicarbonate and extracted with three 50-mi portions of ether. The combined ether extracts were concentrated at reduced pressure on the steam bath.18 If the residue contained a mixture of solid and an oil, it was washed with 10 ml of cold (0°) methanol and filtered immediately. If a solid was not (18) Conveniently, crystallization was found to be hastened if the ether extracts were not dried before removal of excess solvents, especially when p-methoxyaryl isoxazoles were synthesized.Kovacs, Mayers, Johnson, Cover, and Ghatak formed, 5-10 ml of methanol was added and crystallization occurred upon refrigeration of the mixture. Recrystallization was effected with ethanol or benzene (see Table I).

Synthesis of selenocysteine peptides and their oxidation to diselenide-bridged compounds

“…Thereby, even the thiol-protecting group was found to exert surprisingly strong effects with a rank order in the rate of epimerization of StBu`Trt``Tacm`Acm`MeBzl. This would suggest that even the p-methoxybenzyl group should favour racemization in a manner similar to the benzyl-type protecting groups [34,35] and in the case of selenocysteine possibly at higher rates than for cysteine residues.…”

Synthesis and biological activities of oxytocin and lysine vasopressin analogs containing glutamic acid γ‐hydrazide in position 4

“…GlyNH,. In brief, these nonapeptides and the other intermediates were assembled in a stepwise manner as described above using the N-hydroxysuccinimide esters of the corresponding Boc-or Z amino acids (5)(6)(7). Yields and physical data are summarized in Table 1.…”

N-Acylation in combinatorial chemistry

“…In liquid-phase, the N-carbobenzoxy-S-benzyl-Lcysteine pentafluorophenyl ester with valine methyl ester gave 90% of the dipeptide in 5 min. 28 The coupling rate constants for other pentahalogenated phenols have also been measured; pentachlorophenyl (PCP) ester took 62 min to obtain 90% of the dipeptide, and it was insoluble in THF. 28 Dipeptide and tripeptide esters can be prepared in high yields with no racemization if pentafluorophenyl esters are initially prepared with DCC and then used for the coupling reaction with amino acids.…”

“…28 The coupling rate constants for other pentahalogenated phenols have also been measured; pentachlorophenyl (PCP) ester took 62 min to obtain 90% of the dipeptide, and it was insoluble in THF. 28 Dipeptide and tripeptide esters can be prepared in high yields with no racemization if pentafluorophenyl esters are initially prepared with DCC and then used for the coupling reaction with amino acids. 29 Oligopeptides have been similarly prepared by a stepwise addition procedure.…”

“…One of the halouronium salts, bis(tetramethylene)fluoroformamidinium hexafluorophosphate (BTFFH) (28), was introduced for the formation of acid fluorides in liquid-and solid-phase peptide synthesis, 63 since Fmocamino acid fluorides have been recognized as good intermediates for peptide coupling reactions. 64 Reactions with bromotris(dimethylamino) phosphonium hexafluoro-phosphate (BroP) (29), bromotripyrrolidino phosphonium hexafluorophosphate (PyBroP) (30) and chloro tripyrrolidino phosphonium hexafluorophosphate (PyClop) (31) have been compared; in reactions of N-protected amino acids and N-methylated amino acids, peptides were obtained in high yields in 60 min with 0-0.3% racemization, but longer reaction time caused 13-18% epimerization.…”