Natural linear triquinanes

Banwell MG, Austin KAB et al (2007) Chemoenzymatic total syntheses of the linear triquinane-type natural products (+)-hirsutic acid and (—)-complicatic acid from toluene. Tetrahedron 63 6388-6403... 

A chemoenzymatic synthesis of the linear triquinane (-)-hirsutene and identification of possible precursors to the naturally occurring (+ (-enantiomer. Tetrahedron, 60 (3), 535-547 (b) Banwell, M.G., Edwards, A.J., Harfoot, G.J., and Jolliffe, K.A. (2002) A chemoenzymatic synthesis of (—)-hirsutene from toluene. Journal of the Chemical Society, Perkin Transactions 1, 2439-2441. 

In conclusion, it is now possible to assemble highly functionalized linear triquinanes from acyclic precursors with high diastereocontrol. The sequence mixing intramolecular cyclizations and a [3-f2] radical annulation appears as the strategy of choice. To probe its versatility, this strategy will have to materialize into total syntheses of natural products. 

Interception of the alkylpalladium intermediate in a Mizoroki-Heck cyclization can be parlayed to introduce an additional stereocentre and increase molecular complexity. Shibasaki and coworkers insightfully recognized that the linear triquinanes represent a prime opportunity for exploring the feasibility of cascade Mizoroki-Heck processes in the context of natural product synthesis, with their studies leading to the first reported asymmetric Mizoroki-Heck cyclization- ) -allyl nucleophilic trapping sequence. 

A palladium-catalyzed cyclization sequence involving a mal-onate anion-based termination step and leading to linear triquinanes has been reported and employed in the synthesis of the sesquiterpene-type natural product ( )-A ( -capnellene (eq 114). i ... 

Figure 1. Representative linear, angular, and propellane triquinane natural products.

Hirsutene (1) and A9(,2,-capnellcnc (2), the parent members of the hirsutane and capnellane families of triquinane natural products, respectively, are isomeric molecules that possess four contiguous stereogenic centers, one of which is quaternary. The linearly fused tricyclopentanoid frameworks of compounds 1 and 2 are obviously very similar, differing only with respect to the positions of the three methyl groups. An asset of Curran s tandem radical cyclization strategy is that it provides a unified entry into a wide variety of linear condensed cyclopentanoid natural products. As a result, it is possible to devise nearly identical retrosynthetic pathways for these structurally related molecules. 

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. 

Triquinanes. A new route to linearly fused triquinanes uses an intramolecular cycloaddition of a nitrone to a double bond (1 — 2). The product is a precursor to the natural product hirsutene (4). 

Triquinanes rank among the most important natural carbon frameworks [12, 19], Angular- and linear-fused carbon skeletons possess three five-membered rings which share one or two carbon-carbon bonds, respectively. Natural products from a wide array of biological sources produce these compounds with a considerable range of functionality. A new radical anion tandem process to prepare two triquinane skeletons, linear and angular, was initiated by the radical anion of strained ring systems... 

This bicyclo[3.3.0]octenone preparation has been employed in numerous natural product syntheses. Scheme 5-4 shows an early adaption of one of the cycloadditions shown in Eq. (53) toward the synthesis of the linearly fused triquinane system in coriolin. The substitutional and stereochemical characteristics built in by the Pauson-Khand process lend themselves to a very efficient approach [120]. Angularly fused triquinanes have also been prepared by closing the third ring onto a bicyclic Pauson-Khand product [121]. 

Polyquinanes. Polycyclic compounds with a skeleton of only 5-membered carbocyclic rings. Among natural products there are some tri- and tetraquinanes derived from the isoprenoid pathway. Different condensation types exist. Triquinanes are often condensed in a linear way, such as capnellene, complicatic acid, the coriolins, the hirsutanes, and phellodonic acid. Different triquinanes are isocomene, modhephene and pentalenene. The only known natural tetraquinanes are the crinipellins, isolated from mushrooms. 

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