| Autor: |
Tomohide Nakata, Shinjirou Tanoue, Mitsutaka Matsuura, Minoru Kitayama, Atsushi Ohigashi, Minoru Okada, Akihiro Okada, Yasuhiro Morinaga, Joji Hayashida, Shinya Yoshida, Shoji Mizobata, Takumi Takahashi, Shigeru Ieda, Kazumi Kawai |
| Rok vydání: |
2017 |
| Předmět: |
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| Zdroj: |
New Horizons of Process Chemistry ISBN: 9789811034206 |
| DOI: |
10.1007/978-981-10-3421-3_16 |
| Popis: |
Here, we describe a challenging scale-up synthesis of the highly functionalized echinocandin ASP9726 (1) starting from the natural product FR901379 (3), the same raw material of micafungin (2). The synthesis demanded various difficult chemoselective transformations due to the complexity and the unique property of the cyclic poly-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 (13) to nitrile (14) was accomplished by the use of EDC ∙ HCl with pyridine. Further, the sequential nitrile reduction and debenzylation was succeeded with Sponge Nickel- Pd/Ccatalyst mixed catalyst condition. Reductive amination between primary amine (16) with dihydroxyacetone (DHA) was accomplished using 2-picoline borane complex in MeOH, yielding 66.6 kg of peptide core unit (17). After the palmityl chain cleavage by bioconversion, the coupling between the core peptide unit (18) and side chain (9) was achieved by tert-butyl amine borane complex. Consequently, highly pure ASP9726 (1) was obtained in a practical manner without using silica gel or ODS column chromatography purification in any step. The number of step was reduced to 10-steps from 14-steps and the overall yield was drastically increased to 13.8% from 0.71% in comparison with the prior synthesis. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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