Theoretical Studies of Autoxidation of 2-Alkylidene-1,3-cyclohexadione Leading to Bicyclic-Hemiketal Endoperoxides

Abstract

Mechanism of the addition of molecular oxygen on the dienolic form of the 2-alkylidene-1,3-cyclohexadione was investigated by quantum chemical calculations using the approximate projection method developed by Yamaguchi. The complete reaction pathway of the formation of the endoperoxide is described. The crossing between triplet and singlet potential energy surfaces has been located. A multireference complete active space self-consistent field calculation has been performed to strengthen the results.

Nonreductive homolytic scission of endoperoxide bond for activation of artemisinin: A parallel mechanism to Heterolytic cleavage

“…[27][28][29][30][31][32][33] The other possibility of artemisinin activation (Figure 1C), that is, the homolytic cleavage of the endoperoxide bond, has also been discussed in the endoperoxide-based G3-factor antimalarial drugs. [34] However, the latter approach, that is, homolytic cleavage of the endoperoxide bonds with biradical intermediate has received very little attention from the community so far, [35][36][37][38] even though the biradical intermediated has been experimentally detected. [39] In this work, we have investigated the activation of artemisinin for both the possibilities i.e., homolytic and heterolytic cleavage.…”

Isolation and Synthesis of Novel Meroterpenoids from Rhodomyrtus tomentosa: Investigation of a Reactive Enetrione Intermediate

“…Enetrione ( 14 ) may serve as a common precursor, allowing access to 5–11 . In line with the G-factor series of endoperoxides, [10] the alkylidene 12 may undergo autoxidation to afford hydroxy-endoperoxide [4b] ( 13 ), which may subsequently undergo Kornblum-DeLaMare rearrangement [11] to 14 (Scheme 1a). A DFT model (B3LYP/6–31G**) of 14 (Figure 3) shows a twisted isopropyl ketone (C 11 -C 12 -C 13 -O 17 = −57.1°) which appears to minimize O-O lone pair interactions.…”