Enantioselective Syntheses of Rigidiusculamides A and B: Revision of the Relative Stereochemistry of Rigidiusculamide A |
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Authors: | Gui‐Yang Chen Huang Huang Dr. Jian‐Liang Ye Dr. Ai‐E Wang Hui‐Ying Huang Prof. Dr. Hong‐Kui Zhang Prof. Dr. Pei‐Qiang Huang |
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Affiliation: | Department of Chemistry and Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005 (P.R. China), Fax: (+86)‐592‐2186400 |
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Abstract: | The first enantioselective synthesis of cytotoxic natural products rigidiusculamides A (ent‐ 21 ) and B ( 8 ) has been achieved by two synthetic routes. The first one is convergent based on the common intermediate 11 , obtained through a high yielding SmI2‐mediated Reformatsky‐type reaction. A highly diastereoselective one‐pot Dess–Martin periodinane‐mediated bis‐oxidation allowed the direct conversion of the diastereomeric mixture of 11 into rigidiusculamide B ( 8 ). Isolation of minor diastereomer 21 , in combination with computational work, allowed us to suggest the structure of the natural rigidiusculamide A to be 21 , as synthesized by the second route. Four diastereomers ( 7 , 7 , 22a , and 22b ) and an enantiomer ( 21 ) of rigidiusculamide A ( 21 ) have been synthesized. On the basis of literature precedents and computational work, a biosynthetic pathway for rigidiusculamides A and B was proposed to account for the opposite configuration at C‐5 of those two congeners. |
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Keywords: | biosynthetic pathways computational chemistry natural products structure elucidation total synthesis |
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