Stereochemical Revision and First Total Synthesis of Renifolin D
Jarish Ahamad1, Faiz Ahmed Khan1
1Department of Chemistry, Indian Institute of Technology Hyderabad, Kandi, Sangareddy 502285, India.
None:
The first total synthesis and stereochemical revision of (±)-renifolin D are reported. This cytotoxic natural product was erroneously assigned a trans stereochemistry in the original isolation report. However, discrepancies between the NMR data of synthetic and reported renifolin D prompted further investigation. Our synthetic efforts revealed that the originally proposed trans stereochemistry is incorrect, and the actual structure possesses a cis stereochemistry. The revised structure was unambiguously confirmed through detailed spectroscopic analysis (1H, 13C NMR, NOESY) and corroborated through comparison with closely related trans/cis Indane derivatives, thereby validating the stereochemical reassignment. The independent total syntheses of both cis (2) and trans (1) isomers of renifolin D were accomplished in 8 steps (16.7% overall yield) and 9 steps (15.7% overall yield), respectively. This work highlights the pivotal importance of total synthesis as a reliable strategy for the structural elucidation of natural products.
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