Synthesis of (+)-Azaspiracid-1

doi:10.1055/s-2007-991211

Synfacts 2007(11): 1117-1117
DOI: 10.1055/s-2007-991211

Synthesis of Natural Products and Potential Drugs

Synthesis of (+)-Azaspiracid-1

Contributor(s):Philip Kocienski

D. A. Evans*, T. B. Dunn, L. Kværnø, A. Beauchemin, B. Raymer, E. J. Olhava, J. A. Mulder, M. Juhl, K. Kagechika, D. A. Favor
Harvard University, Cambridge, USA
Total Synthesis of (+)-Azaspiracid-1. Part II: Synthesis of the EFGHI Sulfone and Completion of the Synthesis
Angew. Chem. Int. Ed. 2007, 46: 4698-4703

Abstract

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Key words

sulfone anions - hetero-Diels-Alder reaction - glyoxylate-ene reaction - directed aldol reaction - cross-metathesis

Significance

<P>(-)-Azaspiracid 1 is a neurotoxin associated with seafood poisoning. The synthesis of the (+)-enantiomer depicted features the deft use of metallated sulfones in two of the key fragment linkage reactions (A+B) and (E+F) and the use of BOX catalysts J, K, and L in the synthesis of fragments F, G, I, and H, respectively.</P>

Comment

<P>A preceding paper (Angew. Chem. Int. Ed. 2007, 46, 4693) described the synthesis of fragment A. The entire synthesis required only 27 linear steps and gave the target in 2.7% overall yield. The first synthesis of (-)-azaspiracid-1 in 39 linear steps was reported by Nicolaou et al. (Angew. Chem. Int. Ed. 2004, 45, 2609).</P>

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