AB-spiroacetal

The C1-C15 fragment of spongistatin 1, comprising the AB-spiroacetal 4,10 exhibits an axial-axial disposition of the two acetal oxygen atoms at C7 and hence benefits from two stabilising anomeric effects (Figure 3). Based on this, it was expected that the correct spiroacetal would be... 

The desired spiroacetal 36 was converted to the TBS ether and the terminal alkene moiety was elaborated to the corresponding ethyl ketone in four steps, to provide the fully-functionalised CD-spiroacetal ketone 5, now ready for aldol union with the AB-spiroacetal aldehyde 4. This route was found to be highly scalable, enabling production of multi-gram quantities of the desired C16-C28 fragment 5 with little need to repeat the synthetic sequence. 

Paterson, I., Oballa, R.M., and Norcross, R.D. (1996) Studies in marine macrolide synthesis Stereocontrolled synthesis of the AB-spiroacetal subunit of spongistatin 1 (altohyrtin A). Tetrahedron Lett., 37, 8581-8584. 

Terauchi, T. and Nakata, M. (1998) Synthetic studies on altohyrtins (spongistatins) synthesis of the C1-C14 (AB) spiroacetal portion. Tetrahedron Lett., 39, 3795-3798. 

Flowers, C.L. and Vogel, P. (2010) Short diastereoselective synthesis of the C1-C13 (AB spiroacetal) and C17-C28 fragments (CD spiroacetal) of spongistatin 1 and 2 through double chain-elongation reactions. Chem. Eur. J., 16,14074-14082. 

HaMm, R., Brimble, M.A., and Merten, J. (2006) Synthesis of the ABC tricyclic fragment of the pectenotoxins via stereocontrolled cydization of a y-hydroxyepoxide appended to the AB spiroacetal unit. Org. Biomol. Chem., 4,1387-1399. 

Terauchi, T, Terauchi, T., Sato, I., Shoji, W., Tsukada, T., Tsunoda, T., Kanoh, N., and Nakata, M. (2003) Formal total synthesis of altohyrtin C (spongistatin 2). Part 1 Aldol approach to unite AB and CD spiroacetals. Tetrahedron Lett., 44, 7741-7745. 

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