Dioxolane ring systems

The dioxolane ring system was also obtained via three-component reactions involving a diazo ester and electron-rich as well as electron-deficient... 

It was determined that the dioxolane ring system of a 1,6-anhydrohexose would serve well as a chiral template for the dioxolane nucleosides. Thus l,6-anhydromannoseii-i2 was chosen for its ease of large-scale preparation and the configuration of its hydroxyl groups at 2,3 and 4 ( 2 and 3 cis, and 3 and 4 trans) which allows for selective protection prior to oxidative cleavage (Fig. 4). 

Ketoconazole. For treatment of systemic mycoses with amphotericin B or miconazole, the patient must be admitted to a hospital. This is not always possible, particularly in areas where systemic mycoses occur frequently, nor is it always desirable, because of the expense. For these reasons, it was desirable to find an antimycotic that combined safety and broad-spectmm activity with oral adraiinistration. Ketoconazole (10), which is orally active, met most of these requirements. This inhibitor of the ergosterol biosynthesis is an A/-substituted imidazole, that differs from its precursors by the presence of a dioxolane ring (6,7). Ketoconazole is rapidly absorbed in the digestive system after oral adrninistration. Sufficient gastric acid is required to dissolve the compound and for absorption. Therefore, medication that affects gastric acidity (for example, cimetidine and antacids) should not be combined with ketoconazole. 

Most of the synthetic approaches toward this ring system utilize N-amino pyridinium salts functionalized at the a-position with a carbonyl group. Thus, the amination of 2-(l,3-dioxolan-2-yl)pyridine with tosyl-hydroxylamine gave 78, whose reaction with urea in the presence of boron trifluoride-acetic acid gave 79, which gave the thermally unstable... 

Evidence for the formation of Meisenheimer-type adducts from a purine system has been obtained by Liotta in two cases.43 The addition of t-BuO to 6-(2-hydroxyethoxy)-9-methoxymethyIpurine in t-BuOH, as monitored by H-NMR spectroscopy, causes an upfield shift of both pyrimidine and imidazole ring protons and the conversion of two absorptions of the methylene protons of the CH2CH2OH group to a broad absorption of the dioxolane ring, in agreement with the formation of the spiro adduct 19. Similarly, adduct 20 was formed from 6-methoxy-9-methoxymethylpurine by slow reaction with MeCT in 7-BuOH. 

Ring systems phenyl, pyridine, pyrane, thiophene, pyrimidine, dioxolan, naphthalene, cyclohexane,. .. and derivatives... 

Heterocycles with two oxygen or sulfur atoms in one of the rings, i.e., dioxane and dioxolanes as well as their thia analogues have not been considered in this chapter many such ring systems are in the carbohydrate series in the form of acetals. 

From the previous sections on theoretical and spectral aspects of 1,3-dioxolanes, it is clear that the ring is conformationally labile and the data are best explained in terms of a freely pseudorotating system with a small energy barrier between conformers (B-80MI43001). The half-chair (39) and envelope (40) forms are the two lowest-energy conformers and it is the interconversion of these structures which best describes the pseudorotation (75JA1358). The X-ray structure of (1) shows the dioxolane ring has a conformation mid-way between these forms. 

The benzodioxole ring system is distributed widely in nature and is found in numerous natural products such as safrole and piperonal, as well as a multitude of alkaloids. 1,2-Dioxolanes are intermediates in the arachidonic acid cascade, which is the biochemical pathway from essential fatty acids to prostaglandins and similar hormones. The endoperoxide PGH2 (121) is believed to be formed on initial oxidation of arachidonic acid (120). PGH2 has a half-life of 4-5 minutes and is transformed enzymatically into prostaglandins, prostacyclin and the thromboxanes. These compounds are mediators for the control of platelet aggregation, blood vessel dilation and smooth muscle contraction. 

The conformational problems posed by six-membered, saturated rings fused to a 1,3-dioxolane ring (bicyclo[4.3.0] system) have been reviewed by Horton and coworkers,85,89b and will not be elaborated here. Careful assessment of the data would appear to favor a flattened-... 

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