Four-ring system

The present review covers the literature to the end of 1967 and all original sources have been consulted. Syntheses of each of the four ring systems are summarized separately, but physical, chemical, and biological properties are considered generally. Many pjTidopyri-midines were initially synthesized for a study of biological activity or physical properties because of the close structural relationship of these systems to the quinazolines (5) and pteridines (6). Recent reviews have discussed these related compounds. 

The anthracyclines represent a broad family of antibiotics that exhibit activity in numerous tumors. The first anthracyclines, doxorubicin (DOX) and dau-notubicin (DNR), were isolated from Streptomyces var peucetius they were shown to be composed of a tetracyclic ring system with adjacent quinone-hydro-quinone moieties, a short side chain with a carbonyl group, and an aminosugar bound to the C-7 of the four-ring system. DOX and DNR only differed in the side chain terminus (-CH2OH in DOX vs. -CH3 in DNR). Second generation anthracyclines, like epitubicin (EPI) and idatubicin (IDA), were obtained after minor chemical modifications of DOX or DNR, respectively (Fig- 1). 

Carbocation formation is initiated by epoxide ring opening in squalene oxide, giving a tertiary carbocation, and this is transformed into the four-ring system of the protosteryl cation by a series of electrophilic addition reactions (see Box 8.3). 

The ester derivative of pyrrolo[l,2- 7][l,2,5]benzothiadiazepine 5,5-dioxide 346 can be bromoacylated and further reacted with benzylamine and reduced to a four-ring system with an annulated piperazine ring (Scheme 73, Section 4.2 (1994JHC867)). 

Quantitative data are available for the solvolysis of l-(2-aryl)ethyl acetates (where 2-aryl = 2-furyl, 2-thienyl, 2-selenienyl and 2-tellurienyl) in 30% ethanol (77AHC(21)119). The rates at 60 °C relative to the thienyl derivative (1) are selenienyl (1.67), furyl (3.03) and tellurienyl (5.63). These data provide a measure of the effectiveness of the four ring systems in delocalizing the positive charge of the intermediate carbonium ions (80). The rates of the 5-methyl substituted compounds relative to the unsubstituted compounds at 25 °C are thienyl (70), selenienyl (23.3), furyl (160) and tellurienyl (11.8). Thus the furyl derivative is most sensitive to the substituent effect and the tellurienyl the least. The effect of benzo fusion on solvolysis rates has also been studied the solvolysis rate of 2-benzo[6]-thienyl-, -selenienyl- and -tellurienyl-ethyl acetates is less than that of the corresponding monocyclic esters by a factor of about 100. 

Aryl-5,6-dihydrobenzo[4,5]imidazo[l,2-C]-quinazolines Isatoic anhydride could also be reacted with amino-, hydroxyl- or thiolanilines to form 2-(2-aminophenyl)benz-imidazoles, oxazoles or thiazoles, Scheme 5.38. In the case of 2-(2-aminophenyl)benzimidazoles (X=N), the product was formed after 3 min at 150°C in acetic acid. The products could subsequently be further elaborated 6-aryl-5,6-dihydrobenzo[4,5]imidazo[l,2-C]quinazolines, a four ring system, was formed by treatment of the 2-(2-aminophenyl) benzimidazole (X=N) with different aldehydes in acetic acid at 150°C for 5 min (J. Westman, and K. Orrling, Personal Chemistry, Uppsala, Sweden, unpublished results). Fifteen compounds were synthesised in 20-75% overall yield. This 3 + 5 min procedure should be compared to the conventional heating protocol developed by Devi and co-workers57, where each reaction step was run overnight to eventually afford the products in only 30-50% yield. 

This family is viewed as an ortho-attack on the 8-position of the isoquinoline ring. This produces a four-ring system known as an aporphine. 

Cholesterol (3-hydroxy-5,6-cholestene) belongs to a family of compounds derived from a fused, reduced, nonlinear four-ring system of cyclopenta(a -phenanthrene. Bile adds, steroid hormones, and vitamin D metabolites are derivisd from diolesterol. 

The steroid hydrocarbon structure may incorporate functional groups such as alcohols, ketones and olefinic linkages, either in the four-ring system or on the side chain originating at C17. Sterol is a term commonly used to describe all steroidal alcohols. Stenols refer to sterols with A 5 or A 7 double bonds, whereas stanols have a fully saturated ABCD ring system (Gagosian and Heinzer, 1979). 

Recently, some work appeared, where the energetic and geometries of defect centers in zeolites in oxidative conditions were reported [21]. In particular, we quote that the sodalite four-ring system, like the one where we found the peroxy-defects, was studied. 

Nonhydrolyzable lipids are not cleaved into smaller molecules by hydrolysis (including acid, saponification, and digestion) because of the absence of ester groups. Three classes of compounds comprise the nonsaponifiable lipids, as shown in the bottom of Fig. 19-1. Steroids contain a four-ring system of three 6-membered rings and one 5-membered ring ... 

Table 5.1-5 Three and four-ring systems, cont. ...

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