Squalenoids

In the synthesis of the squalenoid glabrescol (72 originally attributed structure), containing five adjacent (all cis) THF rings, the necessary precursor of the polyepoxide cascade, the pentaepoxide 71, was achieved by epoxidation of each of the trisubstituted double bonds of the known (R)-2,3-dihydroxy-2,3-dihydrosqualene (70) by the Shi epoxidation approach (Scheme 8.18) [34]. Treatment of 71 with CSA at 0 °C and subsequent purification by column chromatography provided the pure polycyclic ether 72 by a cascade process reasonably initiated by the free secondary alcohol functionality [35a]. 

Cyclization of Squalene-like Substrates. Ultrasonically stimulated BY is a source of sterol cyclase, which catalyzes the cyclization of squalene oxide and squalenoid compounds to lanos-terol derivatives (eq 13). ... 

Grosa, G., Viola, F., Ceruti, M., Brusa, P, Delprino, L., Dosio, F., and Cattel, L., Synthesis and biological activity of a squalenoid maleimide and other classes of squalene derivatives as irreversible inhibitors of 2,3-oxidosqualene cyclase, Eur. J. Med. Chem., 29, 17, 1994. 

Xiong ZM, Corey EJ (2000) Simple Total Synthesis of the Pentacyclic Cs-Symmetric Structure Attributed to the Squalenoid Glabrescol and Three Cs-Symmetrie Diastere[Pg.165]

Since the 1980s, these brominated squalenoids have been identified in several other Laurencia species collected in all the world s oceans (Canary Islands, Japan, Vietnam),... 

Intricatetraol is airrently the only squalenoid carrying both chlorine and bromine. A biogenetic scheme has been suggested from (6S,7S,10R,HR,14R,15R,18S,19S)-tetraepoxy-squalene (Figure 13.24 Suzuki et al, 1993a). 

The biogenesis of martiriol and other similar structures would also imply (6S,7S,10R,11R,14R,15R,18S,19S)-tetraepoxysqualene, which is regarded as the common intermediate for aU these squalenoid polyethers (Manri-quez et al, 2001). 

Martiriol and a few other non-halogenated cyclic ethers have also been identified in several species of Laurenda. The first to have been isolated is teurilene, a tricyclic squalenoid from a Japanese variety of Laurenda obtusa (Suzuki et al., 1985).It is a meso compotmd, optically inactive by internal symmetry, and strongly cytotoxic with an ED50 of 0.18 pgml against leukemia P-388. A compound very similar to the latter, emylene, was discovered later in a plant of the family Simaroubaceae, Eurycoma longifolia (Morita et al., 1993). 

In 2001, a whole new series of brominated squalenoids was discovered in Chondria armata harvested in the Indian Ocean, off the coast of Goa. Armatols A-F differ from their analogs in Laurenda by the quasi-general presence of two bromines (one at each end of the molecule), involving a double cyclization induced by a bromonium ion. Another difference lies in the presence of several cyclic ethers with seven elements (oxepane) (Ciavatta et al., 2001). Armatols also have antiviral, antibacterial, and antifungal properties. OH... 

NHCHO) squalenoids pyrrole, imidazole and indole alkaloids cyclic peptides... 

Terpenes squalenoids aromatic derivatives heterocyclic compounds... 

Figure 19.53 Sodwanones, yardenones and related squalenoids of Axinellidae.

Figure 19.77 Triterpenic glycosides (squalenoids) of Haplosclerid sponges.

Raspailiidae Raspailia, Raspaciona Acetylenic derivatives, diterpenes, squalenoids, nitrogen-containing meroterpenes... 

The raspacionins form a series of squalenoids related to the sipholane group (see above), and were all extracted from the same Mediterranean species, Raspaciona acu-leata. Difficult stereochemistry problems have necessitated the use of several techniques (X-ray diffraction, high-resolution NMR, circular dichroism). Some of these triterpenes are presented in Figiue 19.89, in chronological order of their discovery and with their final stereochemistries. 

Figure 19.89 Examples of raspacionins squalenoids of Raspaciona aculeata.

It was probably from a species of this genus that the first non-squalenoid triterpenes were isolated (mokupalides). 

Squalenoid triterpenes are particularly rare in dictyocer-atid sponges, the first and maybe the only known example being a 7,18-diketosqualenoid isolated from an Indonesian Hyrtios erectus. The absolute configtiration was shown to be R,R by synthesis (Williams, Tahir, and Andersen, 1999 Enders and SchiiReler, 2002). 

Little work has been devoted to the class Gastropoda, from which only a few derivatives have been isolated. Limatu-lone is a bicydic triterpene of the squalenoid type produced by the limpet Collisella limatula for protection against predation by crabs and fish (Albizati, Pawhk, and Faulkner, 1985 Pawlik, Albizati, and Faulkner, 1986). Despite the presence of four asymmetric carbon atoms, limatulone is optically inactive and it was determined by total synthesis that natural limatulone contains both the meso derivative and the racemic mixture (Mori, Takikawa, and Kido, 1993). 

All carbon skeletons shown in Figure 23.9 were formd in different species of Laurencia (Chapter 13). Aurilol and auriculol are both cytotoxic to human adenosarcoma HeLa 3 (cervix) cells, with IC50 values of 4.3 and 6.7 pgml, respectively. Aplysiols A and B (Figure 23.9) are rare squalenoids isolated from an opisthobranch mollusk. 

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