title: 3-Dimethylphosphinothioyl-2(3H)-oxazolone (MPTO), a promising new reagent for racemization-free couplings.
abstract: 3-Dimethylphosphinothioyl-2(3H)-oxazolone (MPTO) was synthesized, and its ability to effect racemization-free couplings and cyclization of a peptide and its C-terminal epimer was examined. MPTO showed good reactivity in aprotic polar solvents such as N,N-dimethylformamide (DMF) and N-methylpyrrolidone. In reactivity MPTO resembles DPPA and dimethylphosphinothioyl azide (MPTA) previously developed by us, but it is much better than these reagents because the side reactions specific to the azide method could be avoided. In coupling of Z-Gly-Val-OH with H-Val-OMe in DMF at 0 degree C, no racemization was observed without use of racemization-suppressing additives. Slight racemization observed at room temperature could be completely suppressed by addition of HOBt but not by HOSu. The utility of MPTO was demonstrated by the synthesis of cyclo-(D-Trp-D-Glu(OBzl)-Ala-D-Val-Leu), an intermediate for an endothelin-binding inhibitor BE 18257A. In a comparative study using DPPA, MPTA and MPTO, no racemization was observed for MPTA or MPTO, while DPPA caused considerable racemization. When MPTO was used in the presence of HOBt rapid cyclization (3 h at RT) occurred to give the optically pure cyclic product.
authors.affiliation: Department of Applied Chemistry, Faculty of Science, Science University of Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Katoh
authors.forename: M
authors.initials: M
authors.lastname: Ueki
mesh_terms: D000595:Amino Acid Sequence; D008969:Molecular Sequence Data; D009946:Organothiophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D010081:Oxazolone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D010456:Peptides, Cyclic / Q000138:chemical synthesis*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D009946:Organothiophosphorus Compounds; D010456:Peptides, Cyclic; D000644:Quaternary Ammonium Compounds; C083994:3-dimethylphosphinothioyl-2(3H)-oxazolone; D010081:Oxazolone; C008313:4-(N-maleimido)benzyltrimethylammonium