Total Synthesis of Nominal Diazonamides-Part 2: On the True Structure and Origin of Natural Isolates

Abstract

Unable to bear the weight of scrutiny, the original structure proposed for (−)-diazonamide A (1) must be revised. A convergent, stereocontrolled total synthesis provided 1, which shows altered physical and spectroscopic characteristics relative to those of a sample of the natural product. Reinterpretation of reported data and new insight indicate that the actual structure of diazonamide A is the aminal-containing (S)-α-hydroxy isovaleric acid conjugate 2. Gratifyingly, a synthetic C11 acetal congener of 2 is, by all biological measures examined, similarly potent and functionally equivalent to the antimitotic natural product. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2001/z18199_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.