Quinone epoxides

Porco, Jr. and coworkers also used this biomimehc domino approach for the synthesis of the quinone epoxide dimer torreyanic acid 7-151 as racemic mixture [67]. This natural product, isolated from the fungus Pestalotiopsis microspora, shows a pronounced cytoxicity to tumor cells. Its retrosynthetic analysis leads to the 2H-pyran 7-152 (Scheme 7.40). As substrate for the domino process, the epoxide... 

All the precursors are easily prepared by epoxidation and alkylation of the Diels-Alder adduct of p-benzoquinone and dimethylfulvene, and subsequent pyrolyses of the precursors in a sealed tube under rather mild conditions to yield these epoxy compounds [20-22]. Although there are other methods to prepare such quinone epoxides and a-epoxycyclohexenones, the advantages of the retro Diels-Alder method are as follows 1. epoxidation of quinone adducts proceeds regioselectively to give an epoxide, in which the more substituted double bond in the starting quinone is epoxidized, 2. the adducts are usually stable, and are able to afford appreciably modified quinone moieties, 3. stereoselectivities are expected in the modification of the ewiAj-adducts. 

In connection with investigations in the vitamin K series and considering the fact that some quinones and quinone epoxides are of importance in metabolic processes, the preparation of chiral quinone epoxides is of great interest. Such compounds were obtained with an e.e. of 45% by epoxidation of quinones using hydrogen peroxide in an alkaline medium in the presence of quininium benzyl chloride (QBC) [5]. 

Quinone epoxides, for example the epoxide of juglone, have been obtained by reaction with sodium perborate.3... 

The quinizarine quinone epoxide 2 (sec p 2783) reacts with the diene 32 bearing a protected x-D-daunosamine as chiral auxiliary and the resulting adduct 33 has been used in the synthesis of daunomycine15. 

The polycyclic aromatic hydrocarbon carcinogens, which are very ubiquitous, are metabolized by the microsomal mixed-function oxidase system of target tissues to a variety of metabolites such as phenols, quinones, epoxides, dihydrodiols and dihydrodiol-epoxides ( ). The mqjor pathway of activation of benzo(a)pyrene (BP) leads to the formation of dihydrodiol-epoxide of BP which interacts predominantly with the 2-amino of guanine of DNA. The dihydrodiol-epoxide of BP appears to be the major ultimate electrophilic, mutagenic, and carcinogenic metabolite of BP ( ). Nevertheless, other metabolites such as certain phenols, epoxides and quinones may contribute to the overall carcinogenic activity of BP. In addition, a free radical mechanism may also be partly involved in its carcinogenic activity. 

Yamamoto Y, Nakajima M, Yamazaki H, Yokoi T (2001) Cytotoxicity and apoptosis produced by troglitazone in human hepatoma cells. Life Sci 70 471 82 Yamamoto Y, Yamazaki H, Ikeda T, Watanabe T, Iwabuchi H, Nakajima M, Yokoi T (2002) Formation of a quinone epoxide metabolite of troglitazone with cytotoxic to HepG2 cells. Drug Metab Dispos 30 155-160... 

We decided to investigate one final substrate that contained our desired side chain for the intramolecular Diels-Alder cycloaddition as well as a small and removable cyano group. Our synthesis is outlined in Scheme 11. Phenol 53 was alkylated with chloroacetonitrile, then condensed to form 2-cyano benzo-furan 54. Subsequent quatemarization to 56 was accomplished with sodium hydride and a bromocrotcMiate (55) electrophile. Following phenol ether deprotection and reduction of the benzylic ketone with sodium borohydride, we were in a position to evaluate the dearomatization step. Unfortunately, all attempts to access the quinone epoxide 58 under classic or modified Adler-Becker reaction conditions failed. With these results, we closed the book on the second chapter in our vinigrol saga and went back to the drawing board. 

The structure of 6-methylsalicylic acid and orsellinic acid, themselves formed from acetate (Birch et al., 1955 Mosbach, 1%0 Birkinshaw and Gowlland, 1962), indicates that they may be the immediate precursors of more complex metabolites. Indeed, whole-cell studies have confirmed that 6-methylsalicylic acid may be metabolized, after decarboxylation, to terreic acid, a quinone epoxide (XXXI), in Aspergillus terreus (Read et al., 1%9) or m-hydroxybenzaldehyde (XXXII) and gentisaldehyde (XXXIII) en route to patulin (XII) in P. patulum (Forrester and Gaucher, 1972a). Moreover, orsellinic acid is readily converted to trihydroxytoluene (XIII) and further hydroxylated products in A. fumigatus (Packter, 1%6, 1968). These inter-... 

Quinone epoxides and 5,6-epoxy-4-hydroxycyclohex-2-enones are now readily prepared by way of retro-Diels-Alder reactions, under mild conditions, as shown in Scheme 14. Yields are generally high, and for quinone itself quantitative ... 

Li C, Johnson RP, Porco JA, Jr., Total synthesis of the quinone epoxide dimer (+)-torreyanic acid application of a biomimetic oxidation/electrocyclization/Diels-Alder dimerization cascade. J. Am. Chem. Soc. 2003 125 5095-5106. 

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