title: Oxyma-B, an excellent racemization suppressor for peptide synthesis.
abstract: Peptide-bond formation is a key process in the synthesis of peptide oligomers. Among the many coupling techniques reported, carbodiimides combine strong acylation potency and smooth reaction conditions and are commonly used in the presence of additives. Recently, ethyl 2-cyano-2-(hydroxyimino)acetate (OxymaPure) has emerged as a highly reactive alternative to the classic and explosion-prone benzotriazolic additives, namely 1-hydroxybenzotriazole (HOBt) and 1-hydroxy-7-azabenzotriazole (HOAt). Here we report on a new oxime additive 5-(hydroxyimino)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione (Oxyma-B). This new additive showed satisfactory solubility in various solvents (DMF, ACN, and THF). It was also more effective in the control of optical purity during the synthesis of Z-Phg-Pro-NH2, Z-Phe-Val-Pro-NH2, H-Gly-Ser-Phe-NH2, H-Gly-Cys-Phe-NH2, H-Gly-Cys(Acm)-Phe-NH2 and H-Gly-His-Phe-NH2 than related Oxyma- and benzotriazole-based reagents. Oxyma-B also proved to be advantageous compared to the related HONM, because the latter cannot be used with the carbodiimide. Furthermore, Oxyma-B showed satisfactory performance in assembling demanding sequences such as the Aib-enkephalin pentapeptide (H-Tyr-Aib-Aib-Phe-Leu-NH2).
authors.affiliation: Catalysis and Peptide Research Unit, School of Health Sciences, University of Kwazulu-Natal, Durban 4001, South Africa. albericio@irbbarcelona.org.
authors.forename: Yahya E
authors.initials: YE
authors.lastname: Jad
authors.forename: Sherine N
authors.initials: SN
authors.lastname: Khattab
authors.forename: Beatriz G
authors.initials: BG
authors.lastname: de la Torre
authors.forename: Thavendran
authors.initials: T
authors.lastname: Govender
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Kruger
authors.forename: Ayman
authors.initials: A
authors.lastname: El-Faham
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
mesh_terms: D000595:Amino Acid Sequence; D001463:Barbiturates / Q000737:chemistry*; D010091:Oximes / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques / Q000379:methods*
chemical_list: C000598598:5-(hydroxyimino)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione; D001463:Barbiturates; D010091:Oximes; D010455:Peptides