A Challenging Synthesis of the Highly Functionalized Echinocandin ASP9726: A Successor of Micafungin

DOI

Search this article

Description

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...

Journal

Details 詳細情報について

  • CRID
    1870865117732562432
  • DOI
    10.1021/op500078y
  • ISSN
    1520586X
    10836160
  • Data Source
    • OpenAIRE

Report a problem

Back to top