Total Synthesis and Electrophysiological Properties of Natural (−)‐Perhydrohistrionicotoxin, its Unnatural (+)‐Antipode and their 2‐Depentyl Analogs

Abstract

SummaryNatural ( -)-perhydrohistrionicotoxin (6a), its unnatural (t )-antipode 6b, (-)-2-depentylperhydrohistrionicotoxin (7a) and its (+ )-antipode 7b have been prepared and characterized. Kishi's lactam 8 reacted with optically active isocyanates, and the mixture of diastereomeric carbamates so obtained was separated and hydrolyzed yielding the optical antipodes of Kishi's lactam in optically pure form. Reduction with LiAlH4 yielded the optically active 2-depentyl analogs, while another sequence already developed in the racemic series afforded the natural toxin and its (+ )-antipode. Some electrophysiological properties of these compounds are presented.Natural histrionicotoxin (1, (-)-HTX) was isolated from extracts of skins of the Columbian poison frog Dendrobates histrionicus by Witkop et al. [l]. HTX represents a spiropiperidine, substituted at C ( 2 ) and C (7) with side-chains containing cis-ene-yne unsaturation (Scheme 1).The absolute configuration of 1 shown in Scheme 1, was deduced from data obtained by a single crystal X-ray analysis of isodihydrohistrionicotoxin hydro- ')

Cyclic Sulfamidite as Simultaneous Protecting Group for Amino Alcohols: Development of a Mild Deprotection Protocol Using Thiophenol

“…We unexpectedly found that cyclic sulfamidite was useful for the simultaneous protection of 1,3-amino alcohol during our synthetic studies on (−)-histrionicotoxin (5, HTX). [25][26][27] Previous synthetic studies conducted by Stork and Zhao 28) as well as our own investigation into the endgame sequence, 29) demonstrated that the highly congested 1,3-amino alcohol of (−)-HTX 235A (1) completely resists protection as its acetonide or carbamate form. However, the protection of the 1,3-amino alcohol was unavoidable in elongating two terminal alkenes to enynes to complete the total synthesis (Chart 2).…”

Sonochemical one pot synthesis of novel spiroacridines catalyzed by magnetically functionalized Fe3O4nanoparticles with chitosan as a reusable effective catalyst

“…[3][4][5] Spiro compounds having cyclic structures fused at a central carbon are of recent interest because of their interesting conformational features and their structural implications on biological systems. [6][7][8] The synthesis of spiro-heterocycles presents an interesting synthetic challenge to organic chemists because of its structural rigidity and complexity. Nitrogen inclosing spiro-heterocycles display remarkable biological properties, and are also frequently observed in natural products such as paraherquamide A, spirotryprostatin A, spirotryprostatin B, mitraphylline, pteropodine, and isopteropodine ( Fig.…”

Synthesis, Molecular Structure and Spectroscopic Investigations of Novel Fluorinated Spiro Heterocycles

“…They also act as nicotinic receptor antagonists and have anticancer, antibiotic and antimicrobial properties. Additionally, a review of the literature has shown that the synthesis of fused or spiro-heterocyclic compounds derived from cycloalkanes has not been explored; however, in many cases, it has been observed that enlargement of the cycloalkane ring size influences the biological effect—cyclododecane derivatives appear to have an advantage in this regard [1,2,3,4,5,6,7,8,9].…”