Terpenoids acrylic

Exposure of rat primary mixed hippocampal cell cultures to either sodium nitroprusside (SNP 100 xM) or 3-morpholinosydnonimine resulted in both a decrease in cell survival and an increase in free-radical accumulation. These SNP-induced events were blocked by either EGb 761 (10 to 100 pg/ml) or its flavonoid fraction CP 205 (25 pg/ml), as well as by inhibitors of protein kinase C (PKC chelerythrine) and 1-type calcium channels (nitrendipine). In contrast, the terpenoid constituents of EGb 761, known as bilobalide and ginkgolide B, as well as inhibitors of phospholipases A [3-[4-octadecyl)benzoyl]acrylic acid (OBAA)] and C (U-73122), failed to display any significant effects. Moreover, EGb 761 (50 pg/ml), CP 205 (25 pg/ml), and chelerythrine were also able to rescue hippocampal cells preexposed to SNP (up to 1 mM). Finally, EGb 761 (100 g/ml) was shown to block the activation of PKC induced by SNP (100 xM). These data suggest that the protective and rescuing abilities of EGb 761 are not only attributable to the antioxidant properties of its flavonoid constituents but also by their ability to inhibit NO-stimulated PKC activity (Figure 36.1). 

CM reactions with terpenoids containing two double bonds such as citronellene are hampered by low yields because of RCM competition among other side reactions. Mauduit et al. performed the CM of several terpenoids with n-butyl acrylate and crotonaldehyde using Hoveyda-Grubbs type catalysts containing an aminocarbonyl function [89]. Yields below 43% were obtained in all cases with 1 mol% catalyst. In contrast to these results, the hydrated masked form of citronellene, i.e., dihydromyrcenol, gave 71% yield of the CM product. It was thus proposed that in order to avoid selectivity problems in the CM of terpenoids containing two double bonds, masked derivatives can be used followed by a simple elimination step to recover the olefin functionality. 

Diels-Alder cycloadditions have greater synthetic flexibility when suitable substituents on the diene are available for elaboration to functionality which is otherwise difficult to build into the structure. To this end, several schemes to novel 1,3-dienes have been described this year. Hagemann s ester (79) is a useful intermediate in synthesis of terpenoids. The ester is now conveniently available by regioselective Diels-Alder reaction of 1-methyl-l,3-bis(trimethylsiloxy)buta-1,3-diene (80) with ethyl acrylate. The yield is 61% overall after 5 days heating in xylene at 170—180 C, followed by hydrolysis of the moisture-sensitive adduct (81). The diene (80) is readily prepared from acetylacetone and trimethylsilyl chloride in the presence of triethylamine-zinc chloride in an ether-benzene mixture. The related diene (82), similarly prepared from 2-formylbutan-3-one, is used to give the useful cyclic dienophile (83). These sequences are outlined in Scheme 18. ... 

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