Triterpenoids acyclic

Steroids are heavily modified triterpenoids that are biosynthesized in living organisms from farnesyl diphosphate (Cl5) by a reductive dimerization to the acyclic hydrocarbon squalene (C30), which is converted into lanosterol (Figure 27.12). Further rearrangements and degradations then take place to yield various steroids. The conversion of squalene to lanosterol is among the most... 

In an approach to the stereocontrolled creation of the acyclic side-chain of tetracyclic triterpenoids and other natural products, Trost and his colleagues have converted the acyclic starting compound (29) into the cyclopropanoid intermediate (31) via the diazo-ketone (30). The key step in the scheme is the cleavage of the cyclopropane with lithium dimethylcuprate to give (32). The stereochemistry at C-7 is determined by the configuration of the double bond in (29). The c.d. and u.v. spectra of a series of triterpenoid olefins have been measured. The Scott-Wrixon rules can be used to correlate the sign of the c.d. curves with molecular structure. A... 

While squalene, the parent of all triterpenoids, is a linear acyclic compound, the majority of triterpeneoids exist in cyclic forms, penta- and tetracyclic triterpenes being the major types. Within these cyclic triterpenoids distinct structural variations lead to several structural classes of triterpenoids. Some of the major structures types of triterpenoids are shown helow. 

The biomitetic polyene cyclizations pioneered by Johnson have culminated in stabilizing the cation404,405 and extension to the syntheses of pentacyclic triterpenoids in one step from an acyclic precursor )406-409. Johnson summarized his 50 years of research in a review410. 

Little work appears to have been carried out with benzeneseleninic anhydride on substrates other than steroidal or triterpenoid compounds, but it seems likely that the stronger conditions required to effect oxidation with this reagent makes it less attractive than Ae two-step procedure described above. Indeed, in the few instances repotted it failed to convert hydrocinnamamitte into ciimamamide, and is said to be of no value for the dehydrogenation of acyclic esters. There are, however, several reports in which either catalytic or stoichiometric benzeneseleninic anhydride has effectively dehydrogenated cyclic ketones in high yield, a typical example being illustrated in equation (12). ... 

Cycloastragenol 13, presents a tetrahydrofuranic ring at C-17, and this presence shifted to considerably weaker field the resonance of the 16a-H (6 4.4-5.0) respect to the chemical shift of the same proton, when a acyclic side chain is present (5 4.58-4.6) [219]. All the tetracyclic triterpenoids with a tetrahydrofuranic ring at C-17 show a base peak at m/z 143 in the mass spectrum (El). This peak results from the cleavage between C-17 and C-20 and suggests the presence of the partial structure A (a 25-hydroxy-20,24-epoxy). Fig.(l). 

Cyclisation of Squaiene.—In higher animals and fungi the first formed cyclic triterpenoid is lanosterol (73). The acyclic precursor squaiene (7) is epoxidised to give (3S)-2,3-oxidosqualene (71) which is then cyclised to lanosterol. Bloch and co-workers have isolated the two enzymes involved from liver tissue and shown that the oxidosqualene cyclase has a molecular weight of about 90,000. 

Squalene [(a//- )-2,6,10,15,19,23-hexamethyl-2.6, 10,14,18,22-tetracosahexaene]. The most important aliphatic, acyclic triterpene, C30H50, Mr 410.73, mp. -4.8 to -5.2 C, bp. 284-285°C, formula, see steroids. S. was first isolated from fish liver oils and later detected in plant oils and human fat. It is composed of 6 isoprene units and is formed from activated acetate ( acetyl-CoA) via mevalonic acid. It is an intermediate in the biosynthesis of all cyclic triterpenoids and thus also of the steroids. Its enzymatic cyclization to IanosteroI or cycloartenoI requires molecular oxygen and proceeds through (35)-squalene 2,3-epoxide. lit. Annu. Rev. Biochem. 14,555-585 (1982)"Chem. Soc. Rev. 20,129-147 (1991) - Kaiier, No. 34 Nat. Prod. Rep. 2, 525 - 5W (1985) Phytochemisby 27,628 (1988) (biosy nthe-sis) Stryer 1995,692-695.-/HS290/29 CASHI-02-4]... 

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. 

Monoterpenoids are composed of two isoprene units (CjoHie) that can be found in various states of oxidation in acyclic, monocyclic, and bicyclic forms. Monoterpenoids can be further classified based on their cyclic carbon systems, with a number of them being pharmacologically active. Sesquiterpenoids compounds (C15H24) contain three isoprene units, occurring in simple to complex mono- and polycyclic rings. Triterpenoids are C30 compounds (CaoHUg) which have wide distribution from more than 40 different carbon skeletons. Carotenes are examples of tetraterpenoids (C40H64). Natural rubber is an example of polyterpenoid which contains many cis-isoprene units. 

The biogenetic-type synthesis of a number of naturally occurring penta-cyclic triterpenoids and steroids from acyclic olefinic epoxide precursors has been achieved. Thus the epoxide (501) is transformed into dl-d-amynn (502) (8%) by SnCl4-MeN02 at 0 °C. ... 

Steroids are plant and animal lipids with a characteristic tetracyclic carbon skeleton. Like the eicosanoids, steroids occur widely in body tissues and have a large variety of physiological activities. Steroids are closely related to terpenoids and arise biosynthetically from the triterpenoid lanosterol. Lanosterol, in turn, arises from cationic cyclization of the acyclic hydrocarbon squalene. 

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