242810-01-1Relevant articles and documents
L-malic acid dimer impurity and preparation method thereof
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Paragraph 0025; 0046; 0049, (2020/05/02)
The invention provides an L-malic acid dimer impurity and a preparation method thereof. The L-malic acid dimer impurity (impurity X) is discovered and separated for the first time, and has a structureshown in the specification. The preparation method of the impurity X comprises the following steps: (1) protecting a carboxyl group at one side of L-malic acid to obtain a compound 1; (2) protectinga carboxyl group at the other side of the compound 1 to obtain a compound 2; (3) hydrolyzing the compound 2 under the condition of acetic acid/water/tetrahydrofuran to obtain a compound 3; (4) dehydrating and condensing the compound 3 to obtain a compound 4; and (5) hydrogenating the compound 4 to remove benzyl groups to obtain the impurity X. The impurity spectrum of malic acid stability researchis expanded, and the improvement of the malic acid quality standard is promoted. The compound property of the L-malic acid dimer impurity is studied, and the L-malic acid dimer impurity has positiveguiding significance for selection of storage conditions of malic acid.
Synthesis and structure reassignment of malylglutamate, a recently discovered earthworm metabolite
Griffith, Corey M.,Feceu, Abigail,Larive, Cynthia K.,Martin, David B. C.
, p. 417 - 421 (2019/02/19)
Malylglutamate, a newly identified metabolite in earthworms, was synthesized using a traditional peptide coupling approach for assembling the amide from protected malate and glutamate precursors. The proposed structure (1) and a diastereomer were synthesized, but their NMR spectra did not match the natural sample. Further analysis of the natural sample using HMBC spectroscopy suggested an alternative attachment of the malyl moiety, and β-malylglutamate (2) diastereomers were synthesized, L,L-2 and D,D-2. NMR spectra were an excellent match with the natural sample, and chiral-phase chromatography was employed to identify (a)-β-l-malyl-l-glutamate (2) as the isomer native to Eisenia fetida.
METHODS AND COMPOSITIONS FOR PREVENTING OPIOID ABUSE
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Paragraph 0468; 0469, (2016/11/28)
Abuse-resistant opioid compounds, drug delivery systems, pharmaceutical compositions comprising an opioid covalently bound to a chemical moiety are provided. Methods of delivering an active ingredient to a subject and methods of preventing opioid abuse are also provided.
Synthesis and organocatalytic ring-opening polymerization of cyclic esters derived from l-malic acid
Pounder, Ryan J.,Dove, Andrew P.
, p. 1930 - 1939 (2011/03/22)
The synthesis of 3-(S)-[(benzyloxycarbonyl)methyl]-1,4-dioxane-2,5-dione (BMD) and 3,6-(S)-[di(benzyloxycarbonyl)methyl]-1,4-dioxane-2,5-dione (malide) from commercially available l-malic acid is reported. Ring-opening polymerization (ROP) studies of BMD are reported showing that the controlled ROP of this monomer is possible in the absence of transesterification side reactions, despite the presence of side-chain esters, using 1-(3,5- bis(trifluoromethyl)phenyl)-3-cyclohexylthiourea and (-)-sparteine to catalyze the polymerization. The ROP of malide with this system was ineffective. Investigation of the effect of initiating species revealed that the electronic nature of the alcohol had a greater effect on the ultimate molecular weight and hence initiator efficiency than steric considerations. Deprotection of the resultant poly(BMD) using H2 and Pd/C resulted in hydrophilic poly(glycolic-co-malic acid)s (PGMAs) that were able to undergo autocatalytic degradation in dilute H2O solution such that complete degradation was observed within 6 days.
