Silylpyrrole Oxidation En Route to Saxitoxin Congeners Including 11-Saxitoxinethanoic Acid.

Saxitoxin (STX) is the archetype of a large family (>50) of architecturally distinct, bisguanidinium natural products. Among this collection of isolates, two members, 11-saxitoxinethanoic acid (11-SEA) and zetekitoxin AB (ZTX), are unique, bearing carbon substitution at C11. A desire to efficiently access these compounds has motivated the development of new tactical approaches to a late-stage C11-ketone intermediate , designed to enable C-C bond formation using any one of a number of possible reaction technologies.

Divergent Synthesis of Natural Derivatives of (+)-Saxitoxin Including 11-Saxitoxinethanoic Acid.

The bis-guanidinium toxins are a collection of natural products that display nanomolar potency against select isoforms of eukaryotic voltage-gated Na ion channels. We describe a synthetic strategy that enables access to four of these poisons, namely 11-saxitoxinethanoic acid, C13-acetoxy saxitoxin, decarbamoyl saxitoxin, and saxitoxin. Highlights of this work include an unusual Mislow-Evans rearrangement and a late-stage Stille ketene acetal coupling.