Synthesis of the C1-C19 Domain of Azaspiracid-34

Azaspiracid-34 (AZA34) is a recently described structurally unique member of the azaspiracid class of marine neurotoxins. Its novel structure, tentatively assigned on the basis of MS and ¹H NMR spectroscopy, is accompanied by a 5.5-fold higher level of toxicity against Jurkat T lymphocytes than AZA1. To completely assign the structure of AZA34 and provide material for in-depth biological evaluation and detection, synthetic access to AZA34 was targeted. This began with the convergent and stereoselective assembly of the C1-C19 domain of AZA34 designed to dovetail with the recent total synthesis approach to AZA3.