Quinone methide Subject

In a recent study, we showed that the more flexible pyrido[l,2-a]indole-based cyclopropyl quinone methide is not subject to the stereoelectronic effect.47 Scheme 7.17 shows an electrostatic potential map of the protonated cyclopropyl quinone methide with arrows indicating the two possible nucleophilic attack sites on the electron-deficient (blue-colored) cyclopropyl ring. The 13C label allows both nucleophile attack products, the pyrido[l,2-a]indole and azepino [l,2-a]indole, to be distinguished without isolation. The site of nucleophilic is under steric control with pyrido [1,2-a]indole ring formation favored by large nucleophiles. 

The GPD monomeric units are derived from DHCA monomer 5 via the action of peroxidase and hydrogen peroxide (Figure 5.12d). The mechanism, via a vinylogous quinone methide, involves two H-radical abstractions. Abstraction from a benzylic CH2 to produce quinone methides from phenoxy radicals has been noted previously [378]. When DHCA is subjected to peroxidase-H202, we found monomeric GPD 2, as well as the range of homo- and crossed-dimers involving DHCA and GPD. 

There is no final consensus on whether procyanidin biosynthesis is controlled thermodynamically or enzymatically. In either case proanthocyanidins are synthesized through sequential addition of flavan-3,4-diol units (in their reactive forms as carbocations or quinone methides) to a flavan-3-ol monomer [218]. Based on the latest findings there is some evidence that different condensation enzymes might exist which are specific for each type of flavan-3,4-diol [64] and that polymer synthesis would be subject to a very complex regulatory mechanism [63]. But so far, no enzyme synthetase systems have been isolated and enzymatic conversion of flavanols to proanthocyanidins could not be demonstrated in vitro [219]. If biosynthesis was thermodynamically controlled, the variation in proanthocyanidin composition could be explained by synthesis at different times or in different compartments [64], The hypothesis of a thermodynamically controlled biosynthesis is based on the fact that naturally and chemically synthesized procyanidin dimers occur as a mixture of 4—>8 and 4—>6 linked isomers in approximate ratios of 3-4 1 [220]. Porter [164] found analogous ratios of 4—>8 and 4—>6 linkages in proanthocyanidin polymers. 

Taxodione (180), a tumor-inhibitory diterpenoid quinone [70] has been the subject of synthetic endeavours [71] because of its unique structure as a quinone-methide and partly because of its tumor-inhibitory activity. Banerjee and Carrasco [72] developed an alternative synthesis of the ketone (179) whose transformation to taxodione (180) has already been accomplished by Matsumoto [73]. The synthetic route for the synthesis of the ketone (179) is described in "Fig (15)". 

To a quartz cuvette fitted with a Teflon stopcock was added 53 mg 2,6-dichloro-benzoquinone and 63 mg phenyl m-xylyl acetylene in CH2CI2 in a 0.1 M solution of each substance under argon. The cuvette was then placed in a clear Dewar flask filled with water at 25°C and irradiated with focused light from a medium-pressure mercury lamp (500 W) passed through an aqueous IR filter and an ESCO 410 nm filter. This ensured that the quinone itself was excited and not the diarylacetylene. After 22 h, the solvent was evaporated, and the residue was subjected to flash chromatography. 1-(3,5-Dimethylphenyl)-l-benzoyl-1-methylene-3,5-dichlorocyclohexa-2,5-dien-4-one was obtained as the major product, which was further recrystallized from acetonitrile, m.p., 191-192°C. The minor product was identified only by GC/MS. The total yield of quinone methide was 88% based on 62% of conversion. 

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