No abstract

The asymmetric amination of epoxides is an effective method to synthesize chiral β-aminoalcohols and their components as pharmaceuticals. We have developed a new catalyst system for the asymmetric amination of 1,2-epoxycyclohexane with cyclopropylamine. We have also found that water-soluble soy polysaccharide (Soyafibe S-DN) functions as a catalyst. This catalytic reaction proceeded under mild conditions in hydrous toluene at 37–40 °C. (1R,2R)-2-(cyclopropylamino)cyclohexan-1-ol was obtained at 64% enantiomeric excess (ee) by the asymmetric amination of 1,2-epoxycyclohexane with cyclopropylamine using this catalyst system; it was also made at >99% ee by purification as the fumarate salt. The catalytic activity of this soluble soy polysaccharide remained unchanged, even when treated with a protease, but its activity disappeared when treated with a sugar chain degrading enzyme. These results indicate that the polysaccharide rather than the protein acts as the catalyst for this reaction. Thus, we have discovered for the first time that polysaccharides can act as asymmetric catalysts for the amination of 1,2-epoxycyclohexane.

This paper describes the scope and limitation of substrates subjected to asymmetric amination with epoxides catalyzed by a soluble soybean polysaccharide (Soyafibe S-DN), which we recently discovered from the reaction of 1,2-epoxycyclohexane with cyclopropylamine. Various meso-epoxides reacted with various amines afforded the corresponding products with good enantiomeric selectivity. Since it was found that pectin was found to have a catalytic ability after screening commercially available polysaccharides, we studied 33 different vegetable powders having pectic substances, and we found that many vegetable powders showed catalytic ability. These results should guide in using vegetable components as low-toxic catalysts for the production of pharmaceuticals.

(R)-2-amino-2-ethoxycarbonylsuccinimide (ASI-2) is a key intermediate used in the pharmaceutical industry and is valuable for the industrial synthesis of ranirestat, which is a potent aldose reductase inhibitor. ASI-2 was synthesized in a process combining chemical synthesis and bioconversion. Bioconversion in this study is a key reaction, since optically active carboxylic acid derivative ((R)-1-ethyl hydrogen 3-benzyloxycarbonylamino-3-ethoxycarbonylsuccinate, Z-MME-AE) is synthesized from a prochiral ester, diethyl 2-benzyloxycarbonylamino-2-ethoxycarbonylsuccinate, Z-MDE-AE, at a theoretical yield of 100%. Upon screening for microorganisms that asymmetrically hydrolyze Z-MDE-AE, Bacillus thuringiensis NBRC13866 was found. A novel esterase EstBT that produces Z-MME-AE was purified from Bacillus thuringiensis NBRC13866 and was stably produced in Escherichia coli JM109 cells. Using EstBT rather than porcine liver esterase (PLE), ASI-2 was synthesized with a 17% higher total yield by a novel method, suggesting that the esterase EstBT is a PLE substitute enzyme and therefore, may be of interest for future industrial applications.