Structure toxicity relationships of synthetic azaspiracid-1 and analogs in mice

Synthetic azaspiracid-1 (AZA-1, 1), 6-, 10-, 13-, 14-, 16-, 17-, 19-, 20-epi-azaspiracid-1 (C1–C20-epi-AZA-1, 2), and twelve truncated azaspiracid-1 analogs (3–14) were synthesized and tested for their toxicity effects in mice. Of these compounds only AZA-1 (1) and its diastereomer C1–C20-epi-AZA-1 (2) exhibited significant toxicity in mice with the latter compound (2) being one-fourth as toxic as the former (1). The lack of toxicity exhibited by the severely truncated analogs (3–14) implies that the entire or at least a major part of the structure of AZA-1 (1) is required for biological activity.