Terpenoids cyclizations

LESBURG, C. A., ZHAI, G. Z., CANE, D. E., CHRISTIANSON, D. W., Ciystal structure of pentalenene synthase Mechanistic insights on terpenoid cyclization reactions in biology, Science, 1997,277,1820-1824. 

Lesburg, C.A., Zhai, G.Z., Gane, D.E. and Ghristianson, D.W. (1997) Grystal structure of pentalenene synthase mechanistic insights on terpenoid cyclization reactions in biology. Science, Til, 1820-4. 

Interest in limonene synthase stems in part from the fact that (-)-limonene is the common precursor of menthol and carvone, respectively, of the essential oils of peppermint and spearmint species (Scheme 6) [79]. The cyclization leading to limonene is the simplest of all terpenoid cyclizations and the reaction has ample precedent in solvolytic model studies [58, 59, 80]. Thus, it is not... 

Open-chain 1,5-polyenes (e.g. squalene) and some oxygenated derivatives are the biochemical precursors of cyclic terpenoids (e.g. steroids, carotenoids). The enzymic cyclization of squalene 2,3-oxide, which has one chiral carbon atom, to produce lanosterol introduces seven chiral centres in one totally stereoselective reaction. As a result, organic chemists have tried to ascertain, whether squalene or related olefinic systems could be induced to undergo similar stereoselective cyclizations in the absence of enzymes (W.S. Johnson, 1968, 1976). 

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 triterpene lanosterol. Lanosterol, in turn, arises from cationic cyclization of the acyclic hydrocarbon squalene. 

Subsequent cyclizations, dehydrogenations, oxidations, etc., lead to the individual naturally occurring carotenoids, but little is known about the biochemistry of the many interesting final structural modifications that give rise to the hundreds of diverse natural carotenoids. The carotenoids are isoprenoid compounds and are biosynthesised by a branch of the great isoprenoid pathway from the basic C5-terpenoid precursor, isopentenyl diphosphate (IPP). The entire biosynthesis takes place in the chloroplasts (in green tissues) or chromoplasts (in yellow to red tissues). 

A similar intramolecular alkylation of arene-ene substrates is catalyzed by RuGl3/AgOTf, providing good to excellent yields of cyclization products (chromanes, tetralins, terpenoids, and dihydrocoumarins).25 This method is applied to the synthesis of tricyclic terpenoids, which are formed in nearly quantitative yields with high stereoselectivities (trans cis various between 99 1 and 99 2), as shown in Equation (24). 

The tandem zirconocene-induced co-cyclization of dienes or enynes/insertion of allyl carbenoid/addition of electrophile is a powerful method for assembling organic structures. Two illustrations of its application are the synthesis of the dollabelane natural product acetoxyodontoschismenol 99 [57,62,63] and the one-pot construction of linear terpenoids 100 (Scheme 3.25) [59,64],... 

Fig. 29 Formation of isomeric decalins [71 ]—[73] by cyclization of a terpenoid alcohol catalysed by antibody HA5-19A4 raised to hapten [82]. The transition state [83a] has the leaving group in the equatorial position, as favoured by the Stork-Eschenmoser...

SnCl4 is also superior to 22 SnCl4, and is effective for the enantioselective cyclization of 2-(polyprenyl)phenol derivatives to give polycyclic terpenoids bearing a chroman skeleton.The synthetic utility of 26 SnCl4 is demonstrated by very... 

Polyene cyclizations have been of substantial value in the synthesis of polycyclic natural products of the terpene type. These syntheses resemble the processes by which terpenoid and steroidal compounds are assembled in nature. The most dramatic example of biological synthesis of a polycyclic skeleton from a polyene intermediate is the conversion of squalene oxide to the steroid lanosterol. In the biological reaction, the enzyme presumably functions not only to induce the cationic cyclization but also to bind the substrate in a conformation corresponding to the stereochemistry of the polycyclic product.21... 

Only two compounds are listed here, in which a flavonol molecule is linked to a biosynthe-tically different product such as a terpenoid (denticulaflavonol Figure 12.9) and a flavonol-lignoid structure isolated from heartwood of Distemonanthus benthamianus (Fabaceae). In addition, the latter taxon accumidates derivatives with a 3-OH-2 -cyclization as mentioned before (see previous section). Earlier, similar substituted flavone-lignoid derivatives named scutellaprostins were reported from Scutellaria spp. (for references see Wollenweber ). 

In a more elaborate and specific synthesis, the terpenoid indole skeleton found in haplaindole G, which is isolated from a blue-green alga, was constructed by addition of a nucleophilic formyl equivalent to enone 6.5A. Cyclization and aromatization to the indole 6.6B followed Hg2 -catalysed unmasking of the aldehyde group[6]. 

The reaction of a bis-alkynic alcohol (103) with aqueous dimethylamine gives dimethyl-aminofuran (104) (74IZV206). trans-Enynols cyclize presumably through a cis intermediate with base (75RTC70) or mercury(II) sulfate, a method used for the synthesis of the terpenoid bilabone (105) (69JOC857). 

The aliphatic alicyclic hydrocarbon precursor is not well recognized as the major aliphatic component in dissolved humic substances, although it was previously postulated to occur (II). This precursor might arise from terpenoid hydrocarbon lipids, but the data presented in this chapter favor polyunsaturated lipid precursors that are oxidatively coupled and cyclized by free-radical mechanisms (20). Degradative studies have not identified this aliphatic component in recognizable fragments. The quantitative, structural-model approach presented here combines the results of 13C NMR, NMR,... 

Terpenoid alcohols, such as 25, are cyclized in superacids (FSO3H/SO2) under amixture of kinetic and thermodynamic control. Intermediate oxonium species were identified by 13C NMR59. 

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