3621-79-2Relevant articles and documents
2-production of diester perglutaric aminomethylene
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Paragraph 0041, (2017/05/30)
PROBLEM TO BE SOLVED: To provide a method enabling production of 2-methylene glutaric acid diesters in higher yields.SOLUTION: This invention is the production of 2-methylene glutaric acid diesters. It consists of a process in which an acrylic ester and a phosphine catalyst are mixed after the acrylic ester is heated and of a process of dimerization of the acrylic ester for the production of 2-methylene glutaric acid diesters.
Prodrug forms of N-[(4-deoxy-4-amino-10-methyl)pteroyl]glutamate-γ- [ψP(O)(OH)]-glutarate, a potent inhibitor of folylpoly-γ-glutamate synthetase: Synthesis and hydrolytic stability
Feng, Yan,Coward, James K.
, p. 770 - 788 (2007/10/03)
Ester prodrugs of the phosphinate pseudopeptide N-[(4-deoxy-4-amino-10- methyl)pteroyl]glutamate-γ-[ψP-(O)(OH)]-glutarate (1a) were synthesized. H-phosphinic acids derived from N-Cbz vinyl glycine esters were converted to the desired pseudopeptides by Michael addition to α-methyleneglutarate esters. Pivaloyloxymethyl (POM) ester moieties were incorporated in both the N-terminal and C-terminal fragments prior to formation of either C-P bond, N-Alkylation of the corresponding amides derived from N-(N-methyl)aminobenzoic acid with 2,4-diamino-6-(bromomethyl)pteridine gave the target compounds. POM esters of methotrexate and the corresponding γ-glutamyl conjugate were also synthesized using the same strategy. All prodrugs were evaluated in Chinese hamster ovary cells. Although the pseudopeptide prodrugs were ineffective, prodrugs of methotrexate and the corresponding γ-glutamyl conjugate were equipotent with the parent compounds. Stability of the prodrugs was investigated in both phosphate buffer and cell line medium to provide a rationale for the observed biological data.
Carbon-13 Labelling Study of the Coenzyme B12-dependent Methylitaconate α-Methyleneglutarate Model Rearrangement Reaction and Examination of Potential Cyclopropane Intermediates
Dowd, Paul,Hershline, Roger
, p. 61 - 70 (2007/10/02)
The model rearrangement mimicking the coenzyme B12-dependent, enzyme-catalysed interconversion of α-methyleneglutaric acid with methylitaconic acid has been carried out with a carbon-13 label.This experiment demonstrates beyond doubt that the acrylate group is the migrating group in the model, as it is in the enzyme-catalysed rearrangement.Experiments designed to probe the possible occurence of cyclopropylmethyl intermediates in the model rearrangement are also described.To this end the cis- and trans-bromomethylcyclopropanediacids (16a) and (20a) were prepared starting from the common precursor cyclopropane-1,1,2-tricarboxylic acid (13).Thus, (13) was converted into the anhydride (14) which was, in turn, reduced to the lactone (15).Opening of the lactone with HBr in acetic acid gave the desired trans-diacid (16a).For the cis-diacid (20a), the anhydride (14) was hydrolysed, esterified with diazomethane, then reduced with lithium triethylborohydride.Conversion of the resulting alcohol (19) into the bromide (20a) was effected with phosphorus tribromide.An extensive series of experiments involving treatment of the acids and their methyl and tetrahydropyranyl esters with vitamin B12s was carried out.No methylitaconic acid (3a) could be detected in any of the reaction mixtures.However, α-methyleneglutaric acid (2a) and methylglutaconic acid (21) were observed as the reaction products.The methyl toluene-p-sulphonate (22) and iodide (23) were also examined and yielded results analogous to those obtained with the bromides.
