Asymmetric Synthesis of Sesaminone:  Confirmation of Its Structure and Determination of Its Absolute Configuration

• Published in: Journal of organic chemistry 1997-10, Vol.62 (21), p.7413-7417
• Main Authors: Maioli, Andrew T, Civiello, Rita L, Foxman, Bruce M, Gordon, Dana M
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo971027c

An asymmetric synthesis of the naturally occurring antipode of the tetrahydrofuran lignan sesaminone ((−)-1) has been achieved. An X-ray crystal structure of the synthetic material validated the structure proposed in the literature for this lignan. Additionally, the absolute configuration of the natural product was established by correlation of the synthetic tetrahydrofuran with the known absolute configuration of l-Phe. The opening of the synthesis was a diastereoselective Evans aldol reaction between N-4-pentenoyloxazolidinone 6 and piperonal. Reduction of the major diastereomer of the aldol product provided enantiomerically pure diol 4. The primary and secondary hydroxyl groups of 4 were protected in tandem to generate silyl ether-MOM ether 9. The vinyl group contained in 9 was then elaborated, via a series of four steps, to aryl ketone 10. This aryl ketone was transformed to a mixture of silyl enol ether stereoisomers (11a,b); TiCl4-mediated activation of the MOM ethers contained in this mixture of enol ethers yielded tetrahydrofuran 12 as the major product. Treatment of 12 with fluoride provided synthetic (−)-1.