Bicyclic 1,3-dihydroxy Compounds

4-Dihydroxy-5-methyiphthalide, a synthetic precursor for mycophenolic acid has been produced in an overall yield of 20% from the isoxazoline shown, used in a masked form, in three reaction stages (ref.42). 

3-Cyano-2,4-dihydroxyquinoline has been simply obtained from isatoic anhydride by reaction with methyl cyanoacetate in dimethylformamide containing triethylamine by stirring at 25-30°C during 1 hour, followed by reaction at 78 C for 2 hours. The mixture was then heated with sodium hydroxide in an autoclave at 150°C (275psi.) for 3 hours to afford the product in 88% yield (ref.43) 

4-ethoxycarbonyl-1,6,8-trihydroxy-3-phenylisoquinoline has been synthesised from diethyl acetonedicarboxylate and 6-methyl-1,3-oxazin-4-one in THF containing potassium t-butoxide by reaction at ambient temperature over 16 hours with formation of an interm iate 2-pyridone in 90% yield. 

This upon treatment with ethanolic sodium ethoxide overnight and then acidification with hydrochloric acid gave the product in 96% yield (ref.44) 

An autoxidative procedure has been described by the initial alkylation of phenol with cyclopentadiene in the presence of phosphoric add at ambient temperature giving 4-(cyclopenten-2-yl)phenol, in more than 80% yield followed by isomerisation in 91% yield to the 1-isomer during 2 hours in refluxing benzene solution with a catalytic quantity of dichlorobis(benzonitrile)palladium(ll). The conjugated product with 30% hydrogen peroxide and hydrochloric add upon stirring at 50°C for 3 hours afforded 1,4-dihydroxybenzene in 92% yield accompanied by cyclopentanone (ref.46). 

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Nine-membered protected guanidine 137 can be readily transferred into corresponding carbamate, which was further oxidized into intermediate hydroxy ketone, which spontaneously forms the bicyclic dihydroxy compound 138 (Scheme 25) <2006JA3926>. 

Oxidation of 2,3-epoxynorbomane to diol, ketohydroxy, and diketone derivatives was studied with RuCyaq. oxidant/CCl -CHjCN (co-oxidant=(I04) , H O, Oxone , (CIO)", (S Og) " (BrO )" was ineffectual) [73]. The system RuClj/aq. Na(10 )/CCl4-CH3CN oxidised substituted epoxides containing bicyclic [2.2.1] heptane skeletons, e.g. exo-2,3-epoxynorbomanes to the corresponding diketo compounds [74]. Stoicheiometric RuOyCCl converted 20,21-dihydroxy-lip,... 

Bicyclic, tricyclic and polycyclic compounds containing 1,4-dihydroxy systems undergo reactions not shown by the parent compound, 1,4-dihydroxybenzene. Naphthazarin together with boron trifluoride etherate in acetic acid following a... 

In the condensation of pyrogallol with 2-methylbut-3-ene-2-ol by warming in 5% aqueous citric acid the main fraction isolat proved to be 7,8-dihydroxy-2,2-dimethylchroman (25%) and a second oily fraction was obtained which appeared to be a mixture of 7,8 ihydroxy-2,2-dimethyl-6-prenylchroman and the linear dichroman since upon refluxing in ethanolic hydrochloric acid the latter was obtained in crystalline form, through cyclisation of the bicyclic to the tricyclic compound (15%). 

Bioconversion of 12,13,17-THOA and DEOA. For the biosynthesis of diepoxy bicyclic unsaturated fatty acid by strain ALA2, we predicted that linoleic acid is converted to 12,13-dihydroxy-9(Z)-octadecenoic acid (12,13-DHOA) and then is oxidized at C-17 to form 12,13,17-trihydroxy-9( -oc-tadecenoic acid. This compound is possibly cyclized to form diepoxy bicyclic products. To prove this cyclization step, we used purified 12,13,17-THOA as substrate. Figure 1 demon-... 

The route to 4-2 outlined here is unlikely to be profitable, because oxidation of Itydrazine leads to diimide, HNNH, rather than the dihydroxy hydrazine 4-4 [49], Precursor 4-3 is appeahng because it might be possible to photochemically extrade the very stable molecule benzene from it, providing 4. However, the bicyclic precursor to 4-5 suffers from the same kind of synthetic problem as 4-4. Indeed, organic compounds with N-O bonds are uncommon, and the synthesis of 4-2 or 4-3 may require some audacity. One unorthodox approach would be the reaction of a hydrazine metal salt ( rather inaccessible species [50]) with an acyl hypohalite [51], e.g. (surprisingly, 4-6 seems to be unknown) ... 

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