Altohyrtin

Several natural products and pharmaceuticals have been made in which a TRAP-catalysed oxidation of a primary alcohol to aldehyde step occnrs, and these are listed in 2.1.3 abscisic acid, altohyrtin A, (+)-arisngacin A, 14-[2H]-arteether (Fig. 2.4), astrogorgin, avermectin-Bla (Fig. 2.6), (H-)-batzelladine A (Fig. 1.13), brevetoxin B, (+)-catharanthin, ( )-epibatidine, 2-epibotcinolide, (-)-7-epicylin-drospermopsin, ( )-epimaritidine, epothilone C, irisqninone (Fig. 2.3), gambieric... 

TOTAL SYNTHESIS OF SPONGISTATIN 1 (ALTOHYRTIN A) A TALE OF TEN ALDOLS... 

This chapter attempts to recount some of the highs and lows encountered during the Paterson group s total synthesis of spongistatin 1/altohyrtin A, an extremely rare marine macrolide with a seductively complex structure in combination with displaying promising anticancer properties. We provide the reader with an emotional roller coaster ride through a project that spanned some 7 years, with early studies aimed at... 

Figure l. Originally proposed structures for spongistatin 1 (1), altohyrtin A... 

Pietruszka J (1998) Spongistatins, Cynachyrolides, or Altohyrtins Marine Macrolides in Cancer Therapy. Angew Chem hit Ed 37 2629... 

Kobayashi, M., Aoki, S., Sakai, H., Kihara, N., Sasaki, T., and Kitagawa, I., Altohyrtins B and C and 5-desacetylaltohyrtin A, potent cytotoxic macrolide congeners of altohyrtin A, from the Okinawan marine sponge Hyrtios altum, Chem. Pharm. Bull., 41, 989, 1993. 

The lability of esters can be easily enhanced by substituting the a-position with electron-with drawing groups. Thus, me thoxy acetate esters hydrolyse approximately 20 times faster than simple acetates and phenoxyacetates hydrolyse 50 times faster.646 Evans and co-workers used ammonia in methanol to remove a me thoxy acetate in the presence of two secondary acetate functions and two TES ethers from intermediate 341.1 en route to the marine antitumour agent Altohyrtin C [Scheme 4.341 J.647 648 Similarly, they used sodium carbonate in methanol to cleave a secondary methoxyacetate in the presence of two methyl... 

Complementing cyclopropanation reactions, the dichlorocyclopropanation of glycals has also been used as a means to introduce methyl groups at sugar C2 positions. An excellent illustration of this strategy was reported in connection with a synthesis of the C29 to C51 fragment of altohyrtin A [64]. 

The reaction of anomeric sulfones with vinyl magnesium bromide in the presence of zinc bromide allows direct vinylation at the anomeric center. This reaction was the starting point of an approach for the synthesis of the C29 to C51 fragment of altohyrtin A [64]. The C29 to C44 (EF) portion of this compound has been prepared by a stepwise sequence involving anomeric cyanation, using the reaction of anomeric acetate in the presence of BF3-Et20. The anomeric cyanide was then elaborated to the Weinreb amide, which was condensed with an appropriate vinylic carbanion representing the C29 to C37 chain [298]. 

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