A Challenging Synthesis of the Highly Functionalized Echinocandin ASP9726: A Successor of Micafungin
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説明
Here, we describe a practical, scalable, and challenging synthesis of the highly functionalized novel echinocandin ASP9726 (1) starting from the natural product FR901379 (3), which is a starting material of micafungin (2). The synthesis includes transformations that address significant synthetic challenges due to the need to control the chemoselectivity of the reactions during modification of the highly functionalized peptide core. In the present study, we discovered an efficient, high-yielding route to ASP9726 (1) that is suitable for large-scale production. Namely, dehydration of carboxamide (14) to nitrile (15) was accomplished by use of EDC·HCl with pyridine. Further, the transformation of nitrile (15) to primary amine (17) was conducted via hydrogenation with Sponge Nickel catalyst without decomposition, followed by one-pot debenzylation with Pd/C. Reductive amination between primary amine (17) with dihydroxyacetone (DHA) was accomplished using 2-picoline/borane complex as a reducing agent in MeOH, y...
収録刊行物
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- Organic Process Research & Development
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Organic Process Research & Development 18 725-738, 2014-05-13
American Chemical Society (ACS)