Synthetic Endeavors toward 2-Nitro-4-Alkylpyrroles in the Context of the Total Synthesis of Heronapyrrole C and Preparation of a Carboxylate Natural Product Analogue
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- 作者：Jens Schmidt ; Christian B. W. Stark
- 刊名：Journal of Organic Chemistry
- 出版年：2014
- 出版时间：March 7, 2014
- 年：2014
- 卷：79
- 期：5
- 页码：1920-1928
- 全文大小：455K
- 年卷期：v.79,no.5(March 7, 2014)
- ISSN：1520-6904
文摘
The synthesis of 2-nitro-4-oligoprenyl-substituted pyrrole derivatives relevant to the heronapyrroles and related natural products was investigated. Among numerous approaches, nitration of a 3-farnesyl-substituted unprotected pyrrole using AcONO2 gave the best results, albeit still with unsatisfactory yield and regioselectivity. Therefore, the synthesis of (鈭?-heronapyrrole C acid, an analogue of the naturally occurring antibiotic heronapyrrole C carrying a bioisosteric carboxylate in place of the nitro group, was examined. In lieu of the unsatisfactory nitration, a regioselective acylation with Cl3CCOCl was carried out (>8:1 regioselectivity, in contrast to the 1:1.3 ratio for the nitration). The trichloromethyl ketone was converted to the desired acid in a haloform reaction at the final stage of the synthesis. Further key steps of the analogue synthesis involved a position- and stereoselective Corey鈥揘oe鈥揕in dihydroxylation and an organocatalytic double Shi epoxidation. A biomimetic polyepoxide cyclization cascade established the bis-THF backbone. Thus, (鈭?-heronapyrrole C acid was synthesized in eight steps (14.5% overall yield) from commercially available starting materials.