Terpenoid intermediates preparation

As exemplified in the present procedure, the reaction has been optimized and extended in scope it affords functionalized benzocyclobutenes as well as substituted isoquinolines in high yields. Benzocyclobutenes have been used as intermediates in the synthesis of many naturally occurring alkaloids, - steroids,polycyclic terpenoids,and anthracycline antibiotics. The traditional routes leading to the preparation of benzocyclobutenes have been... 

Cathenamine (100) has been identified as an early intermediate in terpenoid indole alkaloid biosynthesis (cf. Vol. 8, p. 27). It has also been isolated from Guettarda eximia. Another alkaloid, 4,21-dehydrogeissoschizine (99), has now been isolated from this plant it is readily converted into (100) in alkaline solution.29 On incubation with an enzyme preparation from Catharanthus roseus cell cultures in the presence of NADPH at pH 7, (99) was converted into ajmalicine (102), 19-ep/-ajmalicine (103), and tetrahydroalstonine (104), which are the normal products with this enzyme preparation. In the absence of NADPH, cathenamine (100) accumulated.30 The reaction to give (100) proceeded linearly with time, and was dependent on the concentration of protein and substrate. No conversion occurred in the absence of enzyme. 

Addition of the a,3 unsaturated anion (21) to the Michael acceptor (22), in which either alkylation or 1,4-addition is possible, affords only the Michael product. Internal alkylation of the intermediate ester enolates leads to cyclopropyl derivatives (equation 7). Terpenoid polyenes are prepared through conjugate addition of the lithiated protected cyanohydrins (23) to dienyl sulfoxide (24 equation 8). ... 

The terpenoid indole alkaloids are a group of plant bases derived by multiple variation on the strictosidine [(79) p. 20] skeleton. Arguably the most important work in the past five years has been done on these alkaloids with enzyme preparations from plant tissue cultures, and the research is of great potential significance for other studies in alkaloid biosynthesis. The results have allowed close definition of the early stages of biosynthesis (this Report, p. 19). Use of crude enzyme preparations in this way has been extended to the study of benzylisoquinoline biosynthesis, with enzyme-catalysed formation of norlaudanosoline-1-carboxylic acid [(57) p. 16] this compound had earlier been identified as the first of the benzylisoquinolines (this Report, p. 15). It seems that amino-acids of this general formula (6) are key intermediates in the biosynthesis of all isoquinoline alkaloids. Lophocereine (7) is exceptional in that two routes (from leucine and mevalonate) may lead to it, only one of which potentially involves an acid like (6). ... 

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. ... 

The ketone fenchone and the alcohols a-fenchol (endo) and /8-fenchol (exo) constitute the fenchane family of bicyclic monoterpenes. Fenchanes are of rather limited distribution in the plant kingdom, and interest in this group of compounds stems primarily from the fact that their carbon skeleton appears to be derived by rearrangement of a pinane-type intermediate (Fig. 5). (-l-)-Fenchone is one of the m or terpenoids of the volatile oil of fennel (Foeniculum vulgare), and soluble enzyme preparations from fennel leaves convert GPP and NPP to fenchol in the presence of Mn and, in the pres-... 

Regio- and enantioselective reduction of diketones have been conducted successfully by biocafalysis. Examples for the reduction of diketones to hydroxyl ketones and diols are shown in Figure 11.11. Figure 11.11a shows the preparation of a key intermediafe for the synthesis of terpenoids by a baker s yeast-catalyzed reduction of a o-cyclohexanedione. DMSO (10%) was used to solubilize the substrate [67]. Figure 11.11b shows the reduction of 3,5-dioxo-6-(benzyloxy)hexanoic acid ethyl ester by Acinetobacter sp. SC 13874 to the corresponding si/n-(3R,5S)-diol, potential intermediates for die s)mthesis of HMG-CoA reducfase inhibitors, in 99.4% ee with 52-74% de depending on substrate concentrations (74% de in 2g/l and 52% de in lOg/1) [66]. After the reaction, XAD-16 resin was added to facilitate the recovery process by adsorbing the product. 

The aromatic rings serve not only to facilitate construction of the key decahydropicene intermediates through the use of a cyclialkylation reaction [R. E. Ireland, S. W. Baldwin and S. C. Welch, J. Amer. Chem. Soc., 94, 2056 (1972)], but also serve as suitable substrates from which to build the terpenoid substitution pattern in the terminal rings. Since the synthesis entails sequential incorporation of the two aromatic rings, this provides an opportunity to differentiate the two terminal oxygen functions (as methoxy and ethoxy) for preparation of the desired 3-alkoxy-10-hydroxy-decahydropicene nucleus (cf. B). 

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