کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5216725 | 1383274 | 2014 | 10 صفحه PDF | دانلود رایگان |
Potentially scalable total synthesis of reblastatin was achieved based on Panek's previous study. Novel and convenient synthetic routes were developed for the known C8-C20 and C1-C7 coupling partners. The challenging C8-C20 fragment was prepared from TBS protected (S)-5-(hydroxymethyl)dihydrofuran-2(3H)-one (6) in nine steps (20% overall yield), and the C1-C7 fragment was synthesized from commercially available 3,4,6-tri-O-acetyl-d-glucal (9) in eight steps (35% overall yield). On a larger scale, Panek's eight-step assembly of the target molecule from the two partners was also slightly modified, giving 45 mg reblastatin (19% overall yield) in the first batch synthesis. Notable feature of our study is the settlement of the C14 chirality through a diastereoselective α-alkylation of 6 followed by a three-step full reduction of the lactone carboxyl, making vastly available 6 a universally applicable C11-C14 synthon for benzenoid/benzoquinone ansamycins.
Journal: Tetrahedron - Volume 70, Issue 18, 6 May 2014, Pages 2982-2991