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Synfacts 2009(12): 1307-1307  
DOI: 10.1055/s-0029-1218335
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Zoanthamine

Contributor(s):Philip Kocienski
F. Yoshimura, M. Sasaki, I. Hattori, K. Komatsu, M. Sakai, K. Tanino, M. Miyashita*
Hokkaido University, Sapporo, Japan; Kogakuin University, Hachioji, Japan
Synthetic Studies of the Zoanthamine Alkaloids: The Total Syntheses of Norzoanthamine and Zoanthamine
Chem. Eur. J.  2009,  15:  6626-6644  
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Publication History

Publication Date:
20 November 2009 (online)

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Key words

zoanthamine - intramolecular Diels-Alder reaction - photooxidation - conjugate addition - copper

Significance

Zoanthamine is a marine metabolite that inhibits phorbol myristate-induced inflammation. It is also an analgesic that inhibits human platelet aggregation. Major challenges in this synthesis were (1) construction of the trans-anti-trans perhydrophenanthrene ABC ring system; (2) construction of the three ring C quaternary centers at C9, C12 and C22; (3) construction of the two quaternary aminal centers.

Comment

The trans-anti-trans ring system in intermediate H was constructed by an exo-selective intramolecular Diels-Alder reaction. Nine of the eleven stereogenic centers were created by dia­stereoselective reactions starting from (R)-5-­methyl-2-cyclohexenone (A) and (R)-citronellal. The synthesis required 43 steps and proceeded in 2.2% overall yield (average 91% yield per step).

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