38231-86-6Relevant articles and documents
A new pre-column derivatization for valienamine and beta-valienamine using o-phthalaldehyde to determine the epimeric purity by HPLC and application of this method to monitor enzymatic catalyzed synthesis of beta-valienamine
Cui, Li,Guan, Xiao-Qing,Liu, Zhang-Min,Fan, Liu-Yin,Li, Qian,Feng, Yan
, p. 347 - 357 (2017)
Valienamine and β-valienamine are representative C7?N aminocyclitols with significant glycosidase inhibition activity that have been developed as important precursors of drugs for diabetes and lysosomal storage diseases, respectively. The quantitative analysis of these chiral compounds is crucial for asymmetric in vitro biosynthetic processes for converting valienone into valienamine epimers using aminotransferase. Here, we developed an efficient and sensitive method for separation and quantitative analysis of chiral valienamine using reversed-phase high-performance liquid chromatography (HPLC) through o-phthalaldehyde (OPA) pre-column derivatization of the analytes. The epimers were derivatized by OPA in borate buffer (pH 9.0) at room temperature for 30 s, separated on an Eclipse XDB-C18 (5?μm, 4.6?×?150?mm) column, eluted with 22% acetonitrile at 30?°C for 18?min, and detected by a fluorescence detector using 445?nm emission and 340?nm excitation wavelengths. The average resolution of the epimers is 3.86, and the concentration linearity is in the range of 0.02–20?μg/ml. The method proved to be effective, sensitive, and reliable with good intra- and inter-day precision and accuracy, and successfully evaluated the enantiopreference and catalytic capability of the potential aminotransferases on an unnatural prochiral substrate, facilitating the design of an asymmetric biosynthetic route for optically pure valienamine and β-valienamine.
Stereoselective synthesis of (+)-valienamine starting from the naturally abundant (-)-shikimic acid
Ding, Wei,Yu, Jiang-Ping,Shi, Xiao-Xin,Nie, Liang-Deng,Quan, Na,Li, Feng-Lei
, p. 1037 - 1042 (2015)
A stereoselective synthesis of the pharmaceutically useful pseudo-aminosugar (+)-valienamine 1 is described. Epoxide 2 was first prepared via four steps in 79.7% overall yield starting from the naturally abundant (-)-shikimic acid. Epoxide 2 was then converted into the vicinal dihydroxyl compound 3 in 96% yield via a highly regio- and stereoselective water-mediated epoxide opening. Compound 3 was transformed into compound 4 in 86% yield over two steps via ester-reduction and benzylation of the three hydroxyl groups. Compound 4 was converted into azido compound 5 in 90% yield via an SN2-type nucleophilic substitution of the OMs leaving group with sodium azide. Ruthenium-catalyzed stereoselective dihydroxylation of compound 5 afforded dihydroxyl compound 6 in 91% yield. Compound 6 was transformed into compound 7 in 92% yield via selective mono-acetylation of the less-hindered hydroxyl group. Dehydration of tertiary alcohol 7 via an acid-mediated elimination furnished olefinic compound 8 in 85% yield. Finally, compound 8 was converted into the title compound 1 in 91% yield over two steps via deprotection and Lindlar-catalyst-promoted highly selective hydrogenation of the azido group (N3) in the presence of a double bond. (+)-Valienamine 1 was thus synthesized starting from the naturally abundant (-)-shikimic acid via 13 steps in 38.3% total yield.
Preparation method of high-purity validamine
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Paragraph 0020; 0021; 0023; 0024; 0052; 0053, (2018/01/12)
Validamine and valienamine are important chemical raw materials but have high separation cost and complex separation process. The invention discloses a preparation method validamine, which includes the steps of: 1) hydrolyzing validoxylamine A through an NBS chemical method by adding the validoxylamine A and NBS to water as a solvent according to certain molar ratio, and performing a reaction for 4 h at 25 DEG C; 2) carrying out adsorption separation to the reaction product through a weak-acidic cation exchange resin, and concentrating the product to obtain a mixture of the validamine and valienamine; 3) under catalysis by a heavy metal catalyst, performing hydrogenation to the mixture, performing adsorption separation to the reaction product through a weak-acidic cation exchange resin, concentrating the product, and vacuum-drying the concentrate to obtain a high-quality validamine sample.
