Hirsutanes

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. 

Diels-Alder reaction. The Diels-Alder reaction of 1 with 2 provides a key step in a total synthesis of alternative mode, the less stable trans-fusion ol the bicyclopcntanc system is formed. The product is converted in two steps into... 

Caryophyllane, Humulane, Africane, Illudalane, Protoilludane, Hirsutane, Vellerane, Pentalane, Senoxydane... 

Humulane, Caryophyllane, Protoilludane, Illudane, Marasmane, Hirsutane... 

The suggested intermediacy of hirsutene (239) in the biosynthesis of the hirsutane sesquiterpenoids has been supported by its recent isolation from Coriolus consors. In addition an alternative synthesis of this compound has been accomplished by the route outlined in Scheme 26. 

Tricyclo[5.3.1.0 ]undecan-8-onewas readily converted to 3,3-dimethyltricyclo[6.3.0.0 ]-undecan-4-one, which contained the basic skeleton of the pentalenolactone family of antibiotics. A pair of isomeric tricyclo[5.3.1.0 ]undec-3- and -4-en-8-ones provided an entry to the triquinane class of natural products they were converted to hirsutanes cis,anti,cis-tricyclo[6.3.0.0 ]undecanes). Mechanistic studies with labeled precursors showed that ring cleavage occurred with inversion of configuration. ... 

C-l and/or C-2 have been converted to sp3 geometry. One possible explanation for this apparent anomaly is to invoke a A1-2 trans- cis isomerization in humulene prior to cyclization. This permits a more favourable interaction between a developing cationic centre at C-4 and the A8-9 double bond. Thus the conformer (375) of isohumulene could serve as a precursor for the protoilludyl-derived metabolites while its enantiomer could proceed to the hirsutane sesquiterpenoids. 

Full details of the total synthesis of the more complex hirsutane sesquiterpenoids coriolin (410) and coriolin B (411) have been published.198 Another route to hirsutic... 

The hirsutane carbon skeleton, which is found in some other antibiotics produced by the Basidiomycetes, is also formed by a sequence of Wagner-Meerwein rearrangements of a protoilludane carbocation via 5.58. Hirsutic acid... 

A representative example for n = 1 is the synthesis of the hirsutane carbon skeleton130. Irradiation of the dicyclopentenylmethane 2 in methanol led to the cis-syn-cis tricyclo[6.3.0.02 6]-undecanone derivative 4. The reaction is presumed to proceed via the highly strained head-to-head adduct 3, this implies the intermediacy of a 1,4-diradical of type B. The intermediate 3 rearranges rapidly via a nucleophilic ring opening by the solvent. 

Intramolecular.—A full account of the synthetic approaches using intramolecular cycloaddition of enones (1) eventually to yield the hirsutane skeleton (2, Scheme 1) has supplemented the material originally published in note form. ... 

Prompted in part by the significant antibiotic and antitumour properties of several members of the hirsutane class of sesquiterpenoids, there has been a dramatic surge in synthetic endeavour towards these compounds. In this context three independent syntheses of hirsutene (302) have been announced in the year under review. The first of these (Scheme 29) involves two key steps. 

The more heavily oxygenated hirsutane sesquiterpenoid, coriolin (307), poses an even more demanding synthetic challenge and here again this daunting task has been accomplished in three beautifully conceived syntheses. The first of these is illustrated in Scheme 32. Only the final step, in the creation of the... 

C15H1JO4, Mr 262.31, oil, [a][>-79°. Sesquiterpenoid of the hirsutane type from cultures of the fungus Stereum complicatum (Basidiomycetes) see also hir-sutic acid. 

Hiptagenic acid, hiptagin see 3-nitropropanoic acid. HIrsutanes. 

C,5H24, Mr 204.36, colorless oil, bp. 123°C(1.33 kPa). Monocyclic sesquiterpene from the essential oils of many plants such as, e.g., cloves, hops, and various Didymocarpus species. a-H. is often accompanied by the isomeric /5-humulene. The completely hydrogenated, monocyclic derivative of H. is humulane. H. is the biosynthetic precursor of various sesquiterpenoids, see hirsutanes, protoilludanes, etc. formed by basidi-omycetes. 

C23H32O6, Mr 404.50, [a]j3 -114° (CHCI3). An anti-biotically active hirsutane derivative from mycelia cultures of the fungus Phellodon melaleucus (Basidio-mycetes). The cytotoxicity as well as the strong anti-... 

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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