Relative and Absolute Configuration of Allohedycaryol. Enantiospecific Total Synthesis of Its Enantiomer

Abstract

The enantiomer of (+)-allohedycaryol, a germacrane alcohol isolated from giant fennel (Ferula communis L.), has been synthesized, thereby elucidating the relative and absolute stereochemistry of the natural product. The synthesis of (-)-allohedycaryol started from (+)-alpha-cyperone (5) which was available in relatively large quantities via alkylation of imine 7 derived from (+)-dihydrocarvone and (R)-(+)-1-phenylethylamine. In a number of steps 5 was converted into the mesylate 4with a regio- and stereoselective epoxidation as the key step. A Marshall fragmentation of 4 was used to prepare the trans,trans-cyclodeca-1,6-diene ring present in allohedycaryol. The conformation of synthetic (-)-allohedycaryol was elucidated via photochemical conversion into a bourbonane system. The synthesis of (-)-allohedycaryol also showed that natural (+)-allohedycaryol has the opposite absolute stereochemistry to that normally found in higher plants.

Synthesis and radical oxidation of steroidal 1-oxo-5α-alcohols

“…Using a method employed earlier to prepare a germacrane alcohol, allohedycaryol, solved the problem. 14 We started (Scheme 2) with the allylic alcohol 7 that has already been described in the literature. 15 Its treatment with o-nitrophenyl selenocyanate proceeded by inverting stereochemical configuration 16 at C-3 to give α-derivative 8.…”

“…Oxidation of this allylic selenide with hydrogen peroxide triggered a [2,3]sigmatropic rearrangement 17 that finally led to compound 9 which has a ∆ 2 -1α-hydroxy functionality. What is remarkable for the rearrangement of such a specific system 14 …”

Syntheses of 7-Substituted α-Cyperone Derivatives for Selective Sigma-1 Receptor over Cannabinoid-1 Receptor Binding Affinities

“…[15][16][17][18][19] In brief, azeotropic imination of (+)-dihydrocarvone and (R)-(+)-1-phenylethylamine followed by alkylation with a slight excess of ethyl vinyl ketone (EVK) in THF at 40 o C produced the Micheal adduct. The resulting adduct was hydrolyzed and then treated with sodium methoxide at room temperature to give an easily separable mixture of α-cyperone 1 and its side product.…”

Substituent influence on the diastereoselectivity of the alkylation of cyclic chiral imines

“…16 Finally, allohedycaryol was prepared by de Groot. 17 The main features of the mechanism of Michael reaction were pointed out by d'Angelo et al 2 Based on the computational work of Sevin et al, 18 and several experimental data it was postulated a compact transition state with concerted internal hydrogen transfer leading to high regio and stereoselectivity.…”