143725-11-5Relevant articles and documents
NOVEL IMINOSUGARS AND THEIR APPLICATIONS
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, (2014/01/08)
Iminosugar compounds are described that have inbuilt delivery features by virtue of covalent incorporation of a tocopherol moiety, or alternative moieties that are analogues of tocopherol or select analogues of cholesterol, or its antagonist “Ezitimibe”;
Large-scale synthesis of the glucosylceramide synthase inhibitor N-[5-(adamantan-1-yl-methoxy)-pentyl]-1-deoxynojirimycin
Wennekes, Tom,Lang, Bemhard,Leeman, Michel,Van Der Marel, Gijsbert A.,Smits, Elly,Weber, Matthias,Van Wiltenburg, Jim,Wolberg, Michael,Aerts, Johannes M.F.G.,Overkleeft, Herman S.
, p. 414 - 423 (2013/01/03)
A synthetic route for the preparation of glucosylceramide synthase inhibitor N-[5-(adamantan-1-yl-methoxy)-pentyl]-1-deoxynojirimycin methanesulfonic acid salt (AMP-DNM) has been developed. Herein we report the development and optimization of this synthetic route from its initial version in an academic research laboratory at milligram-scale to the final optimized route that was implemented in a cGMP miniplant on kilogram-scale. The definitive route starts with the separate synthesis of building blocks 2,3,4,6-tetra-O- benzyl-1-deoxynojirimycin and 5-(adamantan-1-ylmethoxy)-pentanal. The aldehyde was synthesized from 1,5-pentanediol in five steps and 45% overall yield. Protected 1-deoxynojirimycin was prepared by a successive hemiacetal reduction/Swern oxidation/double reductive amination sequence of 2,3,4,5-tetra-O-benzyl-D-glucopyranose in 52% overall yield. Reductive amination of the two building blocks produced the benzylprotected penultimate that was isolated as its crystalline (+)DTTA salt in 68% yield. Hydrogenolysis of the penultimate and crystallization of the end product as its methanesulfonic acid salt produced AMP-DNM in 76% yield with a purity of >99.5%. The described route enables the production of multikilogram amounts of inhibitor AMP-DNM as a stable crystalline solid with high purity under cGMP control.
