Brevetoxin B (compound 2) is produced by Ptychodiscus

Chapter 13, Problem 13.72

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Brevetoxin B (compound 2) is produced by Ptychodiscus brevis Davis, a marine organism responsible for red tides. Brevetoxin B is a potent neurotoxin, as a result of its ability to bind to sodium channels and force them to remain open. Its biological action, together with its complex architecture, has made it an attractive synthetic target. During K. C. Nicolaous synthesis of brevetoxin B, the K ring was assembled via the construction of compound 1. The syn disposition of the hydroxyl group and the silicon-based protecting group in 1 was established via the successful conversion of a small amount of 1 into 5, as shown below (J. Am. Chem. Soc. 1989, 111, 66826690). Note that the conversion of 3 to 4 involves the selective tosylation of the primary hydroxyl group: O O O O O O O O O O O HO H H H H H H Me H H H O H O Me H H Me Me H H H Me H Me Me 2 (Brevetoxin B) K J I E F G H CBA D 1 5 3 TBAF O O H HO 4 TsCl pyridine O O O H H NaOMe K O Si R R R (a) Draw the structures of 3 and 4. (b) Draw a mechanism for the conversion of 4 to 5 upon treatment with NaOMe. (c) Explain why the successful conversion of 1 to 5 verifies the syn relationship between the hydroxyl group and the silyl protecting group in 1.