Triterpenes, synthesis

The dammarenyl cation (21) represents the first branch point from which numerous mechanistic pathways of triterpene synthesis diverge. A detailed and interesting study of molecular modelling and conformational analysis indicates that the formation and... 

Structure at the starred position. Kametani has applied his o-quinodimethane approach to pentacyclic triterpene synthesis, and an interesting variant has come from Funk and Vollhardt in a paper which also illustrates the use of a metal (cobalt) in synthesis. The key step in their steroid route is shown in Scheme 3, proceeding via benzocyclobutene and ( -quinodimethane intermediates in analogy with the work of Kametani et al. Perhaps, one day, computers will suggest routes like that of Scheme 3 ... 

Studies by Croteau and Loomis (1973) demonstrated that triterpene synthesis was a rapid process. They fed [2- K ]MVA to peppermint cuttings and followed the label in triterpene and sterol fractions over a period of 12 h. Squalene label peaked after 1 h, stayed at this level for 3 h, and then dropped rapidly. During the peak period, 15-18% of the administered R-MVA label was recovered in squalene. Sterols, and other triterpenes, were labeled more slowly. The labeling kinetics were consistent with the known precursor role of squalene. 

Squalene is also an intermediate in the synthesis of cholesterol. StmcturaHy, chemically, and biogeneticaHy, many of the triterpenes have much in common with steroids (203). It has been verified experimentally that squalene is the precursor in the biosynthesis of all triterpenes through a series of cyclization and rearrangement reactions (203,204). Squalene is not used much in cosmetics and perfumery formulations because of its light, heat, and oxidative instabiUty however, its hydrogenated derivative, squalane, has a wide use as a fixative, a skin lubricant, and a carrier of Hpid-soluble dmgs. 

Epoxyfarnesol was first prepared by van Tamelen, Stomi, Hessler, and Schwartz 4 using essentially this procedure. It is based on the findings of van Tamelen and Curphey5 that N-bromosuccinimide in a polar solvent was a considerably more selective oxidant than others they tried. This method has been applied to produce terminally epoxidized mono-, sesqui-, di-, and triterpene systems for biosynthetic studies and bioorganic synthesis.6 It has also been applied successfully in a simple synthesis of tritium-labeled squalene [2,6,10,14,18,22-Tetracosahexaene, 2,6,10,15,19,23-hexamethyl-, (all-E)-] and squalene-2,3-oxide [Oxirane, 2,2-dimethyl-3-(3,7,12,16,20-pentamethyl-3,7,ll,-15,19-heneicosapentaenyl)-, (all-E)-],7 and in the synthesis of Cecropia juvenile hormone.8... 

NATURAL DITERPENE AND TRITERPENE QUINONE METHIDES STRUCTURES, SYNTHESIS, AND BIOLOGICAL POTENTIALS... 

Despite the broad medical potentials reported so far, the total synthesis of triterpene QMs is yet to be reported. On the contrary, the biosynthesis of triterpene QMs has recently been validated as from the oxidosqualene 88 (Scheme 8.16) in the plants including Maytenus aquifolium and Salacia campestris.10S With the assistance of HPLC analysis and isotopic labeling, it was found that triterpene QMs 90 were formed only in the root of these plants from friedelin 89 and similar cyclized intermediates, which were synthesized in the leaves from oxidosqualene by cyclase. 

Optically active (35)-form, 195, is a key intermediate in the biochemical synthesis of triterpenes and sterols in vertebrates, plants and fungi164. 

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... 

A good example of the simplicity and power of the chemistry to rapidly construct complex systems is provided by the Kolbe dimerization of (55) as the key step of a total synthesis of the triterpene (+)-Q -onocerin (57 Scheme 14) [33], Thus, oxidation of (+)-hydroxy keto acid (55) in methanol containing a trace of sodium methoxide and at a temperature of 50 C, followed by acylation and chromatography, provided (+)-diacetoxydione (56) in a 40% yield. 

The synthesis of 4-aza triterpenic derivative 362 (ring A modification) made use of the oxime rearrangement to promote the lactam formation (equation 141). Again, only one isomer of the product was observed. 

As part of the total synthesis of the triterpene (+)-a-onocerin, one of the first total syntheses in which RuO played a key role, a diphenylethyleneacetoxyketone was oxidised to the corresponding acetoxyketoacid by RuO /aq. Na(10yacetone. Aromatic ring oxidation was also involved (cf. 3.3.1 below) [219]. An oxidative cyclisation of a 1,5-diene to a diol by RuCl3/Na(10 )/wet SiO /THF formed part of the synthesis of the antitumour agent cw-solamin [220]. 

Yeast does not synthesise cycloartenol or triterpenes, and so approaches to clone plant OSCs by complementation in S. cerevisiae are not feasible because of the lack of appropriate mutants. However, LS-deficient yeast mutants accumulate high levels of 2,3-oxidosqualene, favouring the synthesis of novel cycfisation products generated by heterologous expression of OSCs. The absence of lano-sterol also facilitates analysis of the reaction products. Corey and co-workers isolated a cDNA encoding Arabidopsis thaliana CS by transforming a plant cDNA expression library into such a yeast mutant and screening protein preparations derived from pools of transformants for the ability to synthesise cycloartenol by TLC [39]. 

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. 

The third and in many ways most creative phase of George Buchi s career had its roots in his doctoral work at ETH, where he had undertaken the synthesis of degradation products of certain triterpenes. Synthetic studies on natural products has always flourished in George s laboratory at MIT, but with his growing interest in complex alkaloid came the opportunity to ex-... 

Double Sharpless epoxidation was also applied to the synthesis of a key intermediate 10 to the meso-compound 11 that is related to teurilene, abioactive polycyclic triterpene isolated from red alga Laurencia obtusa,4 The reaction of ( , )-Bisallylic alcohol 9 gave the bisglycidic alcohol 10 with 80% de and 89% ee for each epoxidation (Scheme 6AA.4). 

Compounds known to behave in this way in vivo are listed in recent reviews in this Series.1 2 The structures of some of the /3-D-glucopyranosiduronic acids isolated from urine have been proved by chemical synthesis.3 A few similar derivatives of flavones and triterpenes have been isolated from plants. D-Glucuronic acid also occurs in mammalian tissues as a constituent of acid mucopolysaccharides (aminodeoxypolysaccharides, containing uronic acid), such as hyaluronic acid, chondroitinsulfate, and heparin,4 and it is a direct precursor of L-ascorbic acid in plants and mammals.6 It is present in many of the plant polysaccharides classified as hemicelluloses6 and gums,7 and it has also been found in certain bacterial polysaccharides.4... 

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