Tetracyclic triterpenes synthesis

Takano et al. 69) exploited the asymmetric aldolization for the synthesis of more functionalized chiral products which possess units suitable for the construction of certain tetracyclic triterpenes, such as gibberellins and kaurenes. They described the enantioselective synthesis of the tricyclic enone (33) from the symmetric triketone (32) and its conversion into the gibbane framework. Again, (S)-proline was used as the catalyst. 

Although previous workers have suggested bacterial synthesis as a possible source of biogenic PAHs in modem sediments, Hase and Hites (1976) have shown that bacteria more likely only bioaccumulate them from the growth medium. Anaerobic aromatization of tetracyclic triterpenes appeared to have been demonstrated by Lohmann et aL (1990) by incubating radiolabeled j8-amyrin. 

One step in the production of (5), a key intermediate in a synthesis of the tetracyclic triterpene a-onocerin, involved allylic oxidation of the a,)3-unsaturated ester (1). This was accomplished with Se02 in boiling acetic acid.18b The unsaturated hydroxy lactone produced (2) was next to be converted into the saturated keto acid (5), presumably by a stepwise process. However, the Israeli investigators were pleas-... 

As part of an investigation into the synthesis of tetracyclic triterpenes of the lanostane (27)-cycloartane (28) group, Packer and Whitehurst described the synthesis of the indan-2-one 29. Compound 29 has potential as a key intermediate in the synthesis of tetracyclic triterpenes, possessing the trans-CD ring junction and a carbonyl suitably positioned for introduction of the side chain at C-17. 

In their continuing work on the synthesis of pentacyclic triterpenes, Ireland s group proposed the tetracyclic ketone 69 as a key intermediate. However, such a structure could also be elaborated to the tetracyclic triterpene, ( )-shionone... 

A. are chemically heterogeneous Important components include amino acids, often nonproteogenic D-amino acids (e.g. in gramicidin), acetate/malonate units (griseofulvin, tetracycline), sugars and sugar derivatives (streptomycin), tetracyclic triterpenes (fusi-dinic acid, helvolinic acid, cephalosporin P,). There are also many Nucleoside A. (see). A. act by various mechanisms Many interfere with protein biosynthesis, but others, e.g. penicillin, inhibit cell wall synthesis in bacteria. 

Lanoatarol, kryptosterol 5a-lanosta-8(9),24-dien-3P-ol, a tetracyclic triterpene alcohol. M, 426.7, m.p. 140 °C, [o]i3 + 60° (CHCI3). L. is also a zoosterol (see Sterols) present in large amounts in the wool fat of sheep. Structurally, it is based on the hydrocarbon 5a-lanostane ring system. It is biosynthesized from squalene, via 2,3-epoxysqualene, and is an important intermediate in the synthesis of all further tetracyclic triterpenes of the lanostane type and of the steroids. 

The biomimetic cationic domino cyclization of an acyclic unsaturated substrate to give the tetracyclic scaffold of triterpenes and steroids is intensively described in the literature.1121 The concept has recently been used by Corey et al. to prepare enanti-opure (+)-dammarenediol II 18 in an exceptional short way.1131 The synthesis demonstrates the power of the combination of cation-olefin polyannulation with the aldol cyclization for tetraannulation (scheme 4). Successive treatment of the acylsilane 13 with 2-propenyllithium 14 and the iodoalkane 15 efficiently yidds the epoxytriene 16. The Lewis acid... 

If as above we simply represent alicyclic rings sharing two Gs by a vertical line, then we can represent the basic tetracyclic structure of lanosterol as G61G61 G6 C5 (noting that there are two double bonds and various alkyl substituents and also a 3-hydroxyl on the first of the alicyclic rings). Many subsequent reactions yield cholesterol, a major triterpene membrane component that modifies the fluidity of animal cell membranes and is a precursor for synthesis of animal bile acids (fat solubilizing amphipathic detergents) plant triterpenes and steroid hormones such as the corticosteroids cortisol and cortisone, the mineralocorticoid aldosterone and the sex hormones testosterone and 17-(3-oestradiol. The structure and bioactivity of the plant terpenes is sketched below. 

An impressive cationic domino polycyclization has been developed by Corey and coworkers in their short and efficient enantioselective total synthesis of aegicer-adienol (1-150), a naturally occurring pentacyclic nor-triterpene belonging to the 3-amyrin family [42]. Thus, the treatment of the enantiopure monocyclic epoxy tet-raene 1-147 with catalytic amounts of methylaluminum dichloride induces a ca-tion-JT-tricyclation by initial opening of the epoxide to form the tetracyclic ketone 1-148 in 52 % yield, and its C-14 epimer 1-149 in 23 % yield, after silylation and chromatographic separation (Scheme 1.37). Further transformations led to aegicer-adienol (1-150) and its epimer 1-151. 

Johnson et al. have investigated the use of alkynylsilanes as terminators in the synthesis of steroids and triterpenes through biomimetic polyene cyclizations. This strategy was used in the stereospecific synthesis of the tetracyclic ketone (81) using an alkynylsilane as a terminator. Thus, treatment of (80) with trifluoroacetic acid under carefully optimized reaction conditions yielded, after hydrolysis of the ortho ester, the tetracyclic ketone (81 Scheme 39). 

Ring opening of tetrahydrofuran to 4-iodobutanol was used as the starting point for a synthesis of the complex tetracyclic picrasane famework of triterpene quassinoids <050L5601>. Acylative cleavage of tetrahydrofuran can be performed under iodine-... 

Terpene synthesis in nature is a complex process involving successive electrophilic additions followed by a variety of skeletal rearrangements, including those of the Wagner-Meerwein variety. These reactions are typically catalyzed by enzymes and are responsible for the wide array of structural diversity in these compounds, including 6-6-6-5 tetracycles, 6-6-6-6-5 pentacycles, 6-6-6-6-6 pentacycles, and the less abundant acyclic, monocyclic, bicyclic, tricyclic, and hexacyclic triterpenoids. Each of the more than 100 triterpene skeletons identified in nature are formed through the involvement of several multifunctional triterpene synthases. 

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