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A Synthetic Strategy for Saxitoxin Skeleton by a Cascade Bromocyclization: Total Synthesis of
Sohei Ueno1, Atsuo Nakazaki1, Toshio Nishikawa1
1Graduate School of Bioagricultural Sciences, Nagoya University , Chikusa, Nagoya 464-8601, Japan.
Abstract:
A new synthetic strategy for the formation of the ABC tricyclic framework of saxitoxin was developed. The BC ring moiety, including a spiro-aminal structure, was first constructed stereoselectively by a newly designed cascade bromocyclization of a readily available internal alkyne bearing guanidine and urea. The A ring was then synthesized by a guanylation of a cyclic urea, easily prepared via the oxidative cleavage of the diol of the cascade product, followed by addition of cyanide. This strategy enables the concise stereocontrolled total synthesis of (+)-decarbamoyl-α-saxitoxinol, which is a naturally occurring saxitoxin analogue.
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