Synthetic route to neurotoxins in the 2,7-epi-histrionicotoxin series

✍ Scribed by E.J. Corey; Yoichiro Ueda; Ronald A. Ruden

• Book ID: 104224256
• Publisher: Elsevier Science
• Year: 1975
• Tongue: French
• Weight: 191 KB
• Volume: 16
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)91120-1

✦ Synopsis

Recent studies1 have resulted in a number of synthetic pathways to the useful neurotoxin uperhydrohistrionicotoxin.

2 We describe here a new entry into the histrionicotoxin ring system using a Mannich-type Spiro cyclization which eventually led to the synthesis of two new biologically interesting substances 2,7-G-perhydrohistrionicotoxin (XVIII) and its dioxa analog (XXI).

AI-Cyclopentenylacetonitrile (I) was converted by standard procedures to the bromide V3 (bp 67-69"/10 mm) in 59% overall yield via intermediates II-IV. Reaction of V with the dianion of methyl acetoacetatc4

(2.0 equiv) in 15% hexamethylphosphoricamide (HMPA) in tetrahydrofuran (THF) afforded VI (77%) which was converted by heating at reflux with pyrrolidine (6 equiv) and acetic acid (0.5 equiv) in benzene (3 hr) to enamine-ester VII. isolated as a crystalline solid (86%) mp 37-39" after rapid passage