Sesquiterpene triquinanes

In the area of stereodefined sesquiterpenic triquinane construction, radical cascades involving one transannular cyclization from cyclooctanyl or cyclooctenyl radicals proved to be very efficient and reliable strategies. 

The synthesis of other angularly fused triquinanes as well as linearly fused sesquiterpenes such as hirsutene and capnellene quickly followed. Many general methods for the synthesis of cyclopentanoid natural products emerged as a result of the target-oriented effort [6]. These accomplishments have been reviewed extensively on numerous occasions [7]. This chapter reviews the history of retigeranic acid from its isolation and structure determination to published approaches to its synthesis and the four total syntheses accomplished to date. 

An intramolecular nitrile oxide cycloaddition also served as the key step in the stereoselective assemblage of the skeleton of angular triquinane sesquiterpenes of the isocomene series. Tetracyclic isoxazoline 203 was obtained from oxime 202 [derived from tetrahydroindandione 201] and on treatment with sodium hypochlorite... 

Intramolecular tandem Michael reaction.1 Angular triquinane sesquiterpenes such as pentalenene (5) have been synthesized from the bis(enone) 1 by an ntramolecular tandem Michael reaction as the key step for conversion to the rncvclic system. Lithium amides, even bulky ones, are not useful for this step, nor > dimethyl-t-butylsilyl triflate. Annelation can be achieved by reaction of 1 with c lSi(CH3)3, zinc chloride, and N(C2H5), at 160° in either toluene or CH2C12. Use... 

The cyclization provides a route to the angularly fused triquinane system of 3, which lacks two of the methyl groups present in the natural sesquiterpene isocomene (4). Cyclization of a suitably substituted enyne for synthesis of 4, however, proceeds in minute yield.3... 

The photochemical transformations of vinylcyclopropanes are of mechanistic interest, but because of the high energy of the reaction intermediates, especially in the triplet manifold, practical applications are scarce. The regio- and stereo-selective aspects are, however, similar to those of the thermal processes. Additional methods that provide for the cyclopentene rearrangement involve the degenerate photochemical rearrangements observed by Wender during meta-photocycloaddition of arenes and alkenes and utilized extensively in the synthesis of triquinane sesquiterpenes. -" -" (See Section 8.1.9 or ref. 41 for a recent summary.)... 

Magnus was the first to develop extensive synthetic applications of the Pauson-Khand preparation of the bicyclo[3.3.0]oct-l-en-3-one system. His efforts amply demonstrate the degree to which the high level of functionality in the Pauson-Khand products can be directly utilized in building more complex structures. A formal synthesis of the antitumor sesquiterpene coriolin illustrates a very efficient sequence for construction of the third ring in the linearly fused triquinane series in the presence of considerable functionality (Schemes 10 and 18). A synthesis of the related triquinane hirsutic acid utilizes the observation that the proper stereochemical relationship between the substituents at C-7 and the ring-fusion carbon (C-5) of the bicyclo[3.3.0]oct-l-en-3-one system, while not controllable in the cycloaddition reaction itself, may be readily established by acid- or base-catalyzed equilibration (equation 54 and Scheme 19). ... 

The capnellene and hirsutene marine sesquiterpenes are ideal candidates for radical cyclizations and both have been elaborated via carbonyl-alkyne cyclizations (equations 141-143). Thus treatment of the ketone (117) with the sodium naphthalene radical anion gives the triquinane (118). Subsequent allylic... 

Pauson-Khand reaction. In the presence of tetramethylthiourea the Pauson-Khand reaction suceeds with enynes in which the double bond is present in a silylcyclopropene unit. It enables a synthesis of the angular triquinane sesquiterpene (-)-pentalenene. ... 

A neat four-step synthesis of the triquinane sesquiterpene hirsutene (4) has been described, which features the novel iodotrimethylsilane induced rearrangement of the dione (1), to (2), as a key step. Reductive methylation of the enone (2) to (3),followed by Wittig methylenation then completed the synthesis. ... 

Although a number of syntheses of the angular triquinane sesquiterpene isocomene (18) have now been published, the synthesis by Dreiding et al. is interesting since it features the sequential alkynone cyclisations (14)— -(15) and (16)——(17) as the two key 5-ring annulation reactions. In a new synthesis of the related sesquiterpene silphinene (23) intramolecular(2+2] photocycloaddition from (19) is first used to elaborate the tricycle (20), which on brief exposure to iodotrimethylsilane produces (21). Reduction of (21) to (22), and functional group elaboration then completed the... 

Photolysis of enaminones 432 gives tricyclic tetrahydropyridones 433 in good yields. Ring-opening of 433 affords bicyclic dihydropyridones 434, Scheme 119. Both 433 and 434 are useful synthons for the preparation of triquinanes and various sesquiterpenes (92TL7347). 

C15H24, Mr 204.36, oil, [a] -145° (CHCI3). The tricyclic sesquiterpene hydrocarbon C. (triquinane, deca-hydrocyclopenta[a]pentalene skeleton) is found in the soft coral Capnella imbricata. C. inhibits the growth of microorganisms and prevents the attachment of larvae to the coral. 

C15H24, Mr 204.36, oil, a sesquiterpene hydrocarbon of the triquinane type from cultures of Streptomyces griseochromogenes and S. UC 5319. It is the first isolable biosynthetic intermediate in the pathway from farnesyl pyrophosphate to the antibiotically active pentalenolactones. ... 

Balme, G. and Bouyssi, D. (1991) Total synthesis of the triquinane marine sesquiterpene ( )A 02) capneUene using apaUadium-catalyzed bis-cyclization step. Tetrahedron, 50,403-14. 

---