Synthetic Studies on the Ingenane Diterpenes. An Improved Entry into a trans-Intrabridgehead System

Abstract

[reaction: see text] The efficient construction of an ingenol intermediate exhibiting "insideminus signoutside" intrabridgehead stereochemistry is reported. The sequence features the net conversion of a cis-intrabridgehead compound into a highly strained trans-species via palladium-mediated isomerization of an allylic epoxide followed by a low-temperature alkoxide-accelerated 1,5-hydrogen migration.

Photochemical Approaches to Complex Chemotypes: Applications in Natural Product Synthesis

“…214,215 Another example of employing dioxenones can be found in the synthesis of perhydrohistrionicotoxin (249). Histrionicotoxin (248) and its derivatives (Figure 12) are powerful neurotoxic alkaloids initially isolated from the Columbian frog Dendrobates histrionicus. 216−218 Initial attempts of synthesizing perhydrohistrionicotoxin (249) by Smith and Koft employed a [2 + 2] photocycloaddition methodology as the key step for assembling the core of perhydrohistrionicotoxin (249).…”

A Ratiometric Fluorescent Probe for Biological Signaling Molecule H2S: Fast Response and High Selectivity

“…In the course of the synthesis of ingenane diterpenes, Rigby and co‐workers isomerized α‐alkenyl epoxides102 on the basis that stereospecific anti ‐elimination of a HPdXL n fragment from an η 3 ‐allylpalladium intermediate could be effected in the presence of base 103. These eliminations can proceed efficiently, leading to the dienols depicted in Equation (70), but are very sensitive to the substitution at C‐9.…”

Pd‐Mediated Reactions of Epoxides

“…[101] In the course of the synthesis of ingenane diterpenes, Rigby and co-workers isomerized α-alkenyl epoxides [102] on the basis that stereospecific anti-elimination of a HPdXL n fragment from an η 3 -allylpalladium intermediate could be effected in the presence of base. [103] These eliminations can proceed efficiently, leading to the dienols depicted in Equation (70), but are very sensitive to the substitution at C-9.…”