Holmes total synthesis

A retro-l,3-dipolar cycloaddition followed by an 1,3-dipolar cycloaddition was used for a highly efficient total synthesis of (-)-histrionicotoxin (4-354) (HTX) by Holmes and coworkers [123]. HTX is a spiropiperidine-containing alkaloid which was isolated by Doly, Witkop and coworkers [124] from the brightly colored poison-arrow frog Dendrobates histrionicus. It is of great pharmacological interest as a noncompetitive inhibitor of acetylcholine receptors. 

In 1937 Holmes and Corbet (1937) were able to crystallize pure retinol from fish liver. A decade later, Arens and Van Dorp (1946) and Isler and his associates (Isler et aL, 1947) succeeded in achieving the chemical synthesis of pure retinoic acid and retinol. Shortly thereafter, the total synthesis of -carotene was also reported (Karrer and Eugster, 1950). 

Macdonald JM, Horsley HT, Ryan JH, Saubern S, Holmes AB. Total synthesis of (—)-histrionicotoxin 285A and ( )-perhydrohistrionicotoxin. Org. Lett. 2008 10 4227-4229. 

Holmes, A.B., Jennings-White, C.L.D., and Kendrick, D.A. (1984) Total synthesis of ( )-trans-maneonene-B. J. Chem. Soc. Chem. Commun.. 1594-1595. 

---