Subscribe to RSS
DOI: 10.1055/s-2006-955760
Synthesis of (+)-Hexacyclinol
Contributor(s):Philip Kocienski, Thomas SnaddonBoston University and University of California, Irvine, USA
Total Synthesis and Structure Assignment of (+)-Hexacyclinol
Angew. Chem. Int. Ed. 2006, 45: 5790-5792
Publication History
Publication Date:
23 January 2007 (online)
Key words
Stille reaction - Diels-Alder reaction - acid-catalyzed rearrangement
Significance
(+)-Hexacyclinol is a metabolite isolated from Panus rudis strain HKI 0254 in 2002. The structure of this natural product has been the cause of recent controversy [Chem. Eng. News 2006, 84 ( 31), 11]. A synthesis of the proposed structure (J. La Clair Angew. Chem. Int. Ed. 2006, 45, 2769-2773) has recently been revised on the basis of calculated 13C NMR shifts (S. D. Rychnovsky Org. Lett. 2006, 8, 2895-2898). This work substantiates the revised structure and relates to a recent biomimetic synthesis of (+)-panepophenanthrin by Porco and co-workers (Angew. Chem. Int. Ed. 2003, 42, 3913-3917) that amply displays the virtues of biomimetic strategy in natural product synthesis.
Comment
Stille coupling of bromide B and vinyl stannane C gave D that, upon silyl cleavage, underwent Diels-Alder dimerization via exo transition state E to afford F. Subsequent treatment with K10 clay induced SN2′ substitution of the allylmethoxy group by the proximal Re face hydroxyl group giving the target.
Reviews
The Stille Reaction, V. Farina, V. Krishnamurthy, W. J. Scott Org. React (N.Y.) 1997, 50, 1-652. Clay and Clay-Supported Reagents in Organic Synthesis, R. S. Varma Tetrahedron 2002, 58, 1235-1255.