Hexahydronaphthalene ring system

The hexahydronaphthalene ring system of compactin has been constructed by a nitrile oxide cycliza-tion strategy (Scheme 24).42 Thus, cyclization of either (83) or (84) via nitrile oxide intermediates led to... 

The structural feature of these compounds is the hexahydronaphthalene ring system which is functionalized with a-methylbutyric acid ester and a P-hydroxy-8-lactone linked by an ethylene bridge. The p-hydroxy-8-lactone portion of these compounds can be easily opened, and it is converted to the 3, 5 -dihydroxyheptanoic acid [22]. This hydroxy acid portion of their structures, which resembles the HMG portion of the HMG-CoA, is responsible for the activity, and it is known to interact competitively with the HMG binding domain of the enzyme active site [37]. 

C24H36O5, Mr 404.55, cryst., mp. 174°C, [a] +323° (CH3CN), a polyketide. M. is a potent inhibitor (K,= 1 nM) of HMG-CoA-reductase, the key enzyme in the biosynthesis of higher terpenes and steroids such as, e. g., cholesterol. It is produced by Aspergillus terreus and various Monascus species. Thus, e. g., the plasma cholesterol concentration (a major risk factor for the occurrence of arteriosclerosis) decreases by ca. 50% in patients under medication with M. In the terpene metabolism HMG-CoA-reductase reduces 3-hydroxy-3-methy Iglutary 1-CoA to mevalonate. M. mimics the substrate and thus leads to inhibition of the enzyme. M. is commercially available under the tradename Meva-cor . M. was the lead structure for numerous synthetic HMG-CoA-reductase inhibitors that are now available or are being developed (Atorvastatin, Cerivastatin, Fluvastatin, Pravastatin, Simvastatin). In these derivatives the hexahydronaphthalene structure is replaced by heterocylic ring systems, see also compactin. 

Occidentalol is a eudesmane-type sesquiterpene isolated from the wood of Eastern white cedar Thuja occldentalis Linn.), and is characterized by the presence of a c/s-fused decalin system and a homoannular 1,3-diene unit in the molecule, an intriguing combination of functional groups rarely encountered in this class of natural products. Three related syntheses of occidentalol, all of which are based on hexahydronaphthalen-2-one intermediates have been reported, and utilize the carbonyl group for introduction of the diene chromophore in ring A 1-3,5 synthesis outlined below, utilizing a c/s-fused decalone derivative (A) illustrates several of the key features of these syntheses. 

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