Synthesis of DL-.gamma.-carboxyglutamic acid derivatives

Abstract

X=P(0)0R1 + R2OH -* CH3C0CH(CH3)0P(0)(0R1)(0R2) (2) Alcohol R^H reacts much faster with X-P(0)0Ar than with the product X=P(0)0R1, and, therefore, the symmetrical phosphates, CH3C0CH(CH3)0P(0)(0R1)2, are not formed in any appreciable extent. Moreover, the phenols with electron -withdrawing substituents are much less reactive than alcohols toward both X=P(0)0Ar and X=P(0)0R1, and hence the corresponding aryl phosphates are not produced.The effective catalysis of reaction 2 by the phenol salts [e.g., a factor of ~140 in the reaction of ¿-C4H9OH with X=P(0)0-c-C5H9 by p-N2C6H4-0(C2H5)3NH+ in 0.2 M CDCI3 at 25°] could involve 5-and 6-coordinate phosphorus intermediates4 4 and 5; the latter, 5, is analogous to compounds isolated from the reaction of stable pentaoxyphosphoranes, phenols and tertiary amines.4,5These results may have a bearing on the mechanism of action of enzymes that catalyze the reactions of phosphates and pyrophosphates, since the presence of tyrosine, lysine, arginine, and histidine residues could facilitate the addition of nucleophiles to 4-coordinate phosphorus by analogous mechanisms.

Palladium(0)-Catalyzed Highly Regio- and Stereoselective Addition of Organoboronic Acids with 1,2-Allenylphosphonates Forming Tri- or Tetrasubstituted 1(E)-Alkenylphosphonates

“…We and Oh et al reported the Pd-catalyzed reaction of allenes with organoboronic acids in the presence of HOAc. − However, the regio- and stereoselectivity or yield is not excellent. On the other hand, phosphonates show very important bioactivities, and 1-alkenylphosphonates are important intermediates in organic synthesis, so highly stereoselective methods for the synthesis of substituted 1-alkenylphosphonates are desirable. Here, we wish to report a highly regio- and stereoselective palladium(0)-catalyzed addition of organoboronic acids with 1,2-allenyl phosphonates in the presence of HOAc forming tri- or tetrasubstituted 1( E )-alkenyl phosphonates.…”

The N-terminal sequences of blood coagulation factor X1 and X2 light chains. Mass-spectrometric identification of twelve residues of γ-carboxyglutamic acid in their vitamin K-dependent domains

“…By mass-spectrometric sequence determination of acetylated permethylated peptides, ten residues of a new amino acid, y-carboxyglutamic acid, were identified in the N-terminal region of bovine prothrombin (Magnusson et al, 1974;Morris et al, 1976); the deduced structure of the new amino acid was proved by synthesis of y-DL-carboxyglutamic acid (Morris et al, 1975;Fernlund et al, 1975). The synthesis and chemical characterization of y-carboxyglutamic acid have been undertaken in several laboratories (Morris et al, 1975;Fernlund et al, 1975;Boggs et al, 1975;Marki & Schwyzer, 1975;Bajusz & Juhasz, 1976;Marki et al, 1976;Weinstein et al, 1976;Marki et al, 1977). The y-carboxyglutamic acid residues arise from a post-translational enzymic y-carboxylation of glutamic acid residues, which requires vitamin K (Esmon et al, 1975), and the polypeptide region thus modified binds Ca2+ ions (Nelsestuen & Suttie, 1972;Stenflo & Ganrot, 1973).…”

Amino acids and peptides. 44. Synthesis of DL-.gamma.-carboxyglutamic acid, new amino acid

“…12 The third path started with the tosylate mentioned above and several DL derivatives of blocked I were generated, but there was no report of the free amino acid. 13 The fourth preparation used a condensation between ethyl N"-acetyl-2-methyleneglycinate and diethyl malonate to yield triethyl DL-acetamidopropane-l,l,3-tricarboxylate. Alkaline hydrolysis, desalting, and treatment with ammonium hydroxide formed the monoammonium salt of the DL amino acid I.…”