Total Synthesis of (+)-Saxitoxin

Keywords

(+)-saxitoxin - pyrrolopurine alkaloids - borylcupration/protonation sequence - [2+2] photocycloaddition - oxidation/retro-aldol reaction - ozonolysis

Significance

Luo and co-workers report the total synthesis of ( + )-saxitoxin, which is a prominent neurotoxin found in shellfish. The authors showcase a novel enantioselective [2 + 2] photocycloaddition strategy to construct the core framework of the natural product. The high stereocontrol is achieved by installment of a chiral alkenylboronate ester, which is a key component for the hydrogen-bond-mediated transition-state stabilization to form the contra-thermodynamic product.

 

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Comment

Alkyne B was synthesized from 8-bromoxanthine in 4 steps. Subsequent borylcupration employing catalytic amounts of CuCl and protonation yielded alkenyl boronate ester C. After transesterification using chiral triol D, irradiation with UV light triggered the key [2 + 2] photocycloaddition to afford cyclobutane intermediate F. Oxidation with hydrogen peroxide followed by a retro-aldol reaction and reduction furnished diol G. ( + )-Saxitoxin was then accessed after functional group interconversions.

 

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Publikationsverlauf

Artikel online veröffentlicht:
22. Mai 2025