Triquinanes structure

Coriolin (689), a metabolite of the Basidiomycete Coriolus consors, has attracted widespread interest because of its unusual anti-tumor activity and highly functionalized triquinane structure. Accordingly, a number of syntheses of689 have appeared on the scene. One of the earliest, due to Tatsuta, et al., begins with epoxide 690, whose preparation had been earlier realized in connection with their work on hirsutine (see Scheme LXIII). Deoxygenation of 690, hydrolysis, and cis-hydroxy-lation provided keto triol 691 (Scheme LXXII) The derived acetonide was transformed via 692 into tetraol 693 which could be selectively acetylated and dehydrated on both flanks of the carbonyl group. Deacetylation of 694 followed by epoxidation completed the synthesis. 

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. 

Sequential pyrrolidine and hydantoin ring-forming reactions via intramolecular [2+3] cycloaddition have been applied to the stereoselective solid-phase synthesis of conformationally constrained tricyclic triazacyclopenta [C]pentalene scaffold 43 < 1999JOC8342>. These novel compounds 43 share the structural complexity characteristic of certain alkaloid natural products, angular triquinanes. The retrosynthetic analysis is shown in Scheme 87. 

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. 

Tricyclodehydroisohumulone (550), detected as a new bittering component present in beer and in stored hops, is formed in low yield by boiling aqueous humulone (549) in air. This highly functionalized triquinane, originally believed to possess an alternative structure is best prepared (30%) by reaction of 549 with lead tetra-... 

An elegant application of this photocycloaddition in the field of triquinane synthesis has been reported by Reddy and Rawal [160]. The initially formed oxetane 163, formed from the Diels-Alder adduct 162, is easily cleaved reductively (by use of LiDBB = lithium di-/er -butyl-biphenylide) to give 164. This approach was also used for the construction of structurally diverse di- and (propellane-type as well as linear or angular anellated) triquinanes [161]. The classic linear triquinane hirsutene is also available via this route [162]. Star-like molecules like the tiene 167 are available via a sequence of intramolecular photocycloaddition (from the 1,3-cyclohexadiene/acylallene adduct 165) and oxetane (166) ring-opening (Sch. 58) [163]. Further examples of intramolecular... 

This concept has been applied for the synthesis of the structurally complex and highly oxyfunctionalized triquinane (—)-coriolin (Sch. 31) [61]. Two carbonyl groups, both in the right position for 1,2-acyl shift were present in the trimethyl-functionalized bicyclo[2.2.2]octenone 58. With a site-selectivity of 85% the expected regioisomeric tricyclic dione 59 was formed as a mixture of epimers (Sch. 31). Subsequent transformations involving the annulations of the third five-membered ring as well as epoxidation and hydroxylation steps led to the desired natural product... 

The versatile applicability of this photocyclization concept was demonstrated through the synthesis of important structural frameworks as for example triquinanes [49a] or furanosides [49b], respectively. 

Briggs et al. proposed a new strategy for the synthesis of tricyclic structures using acyl xanthates as precursor for acyl radicals [121]. Irradiation with visible light of a solution of acyl xanthate in presence of 1,6-diene 126 afforded czs-fused bicyclic compound 127 in a good yield (Scheme 38). Radical reduction of xanthate and subsequent aldol condensation leads to the formation of [5.5.5]-fused ring systems similar to those of the triquinane terpene family. 

Another major tricyclopentanoid structural motif, the tricyclo[6.3.0.(P ]undecane skeleton of the so-called linearly fused triquinanes, is also readily accessed by using the meta cycloaddition process, as... 

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). ... 

Since our direct route to angularly fused triquinanes from cycloaddition of l-(4-pentynyl)cyclopen-tenes is limited to trisubstituted alkenes and simple terminal alkynes, bisnorisocomene, but not iso-comene itself, could be prepared (Scheme 22). However, this limitation is not a factor for most other compounds in this class of natural products, and the steric interactions described earlier worked to our advantage in a diastereocontrolled synthesis of pentalenene (see structure. Scheme 20). The natural product was obtained by subjecting the product of Scheme 14 to the sequence i, Li, NH3, MeOH ii, MeLi, Et20 iii, p-TsOH, benzene, reflux. ... 

C,sH24, Mr 204.36, oil, bp. 65-70°C (33.3 Pa), [aJo -15.8° (CHCI3). A natural triquinane hydrocarbon with a [3.3.3]propellane structure from Isocoma wrightii (Asteraceae), an indigenous species of south west USA toxic to cattle and sheep, from South African Berkheya species, and the roots of Senecio isatideusK Derivatives of M. show antiproliferative activity. ... 

The diastereoselective construction of polycyclic structures such as linear triquinanes has been explored by the Malaciia group from acychc or macrocyclic precursors. Based on an acyclic (bromomethyl)dimethylsilyl precursor, the outcome of the sequence leading to the triquinane is remarkable five new C-C bonds, two contiguous quaternary centers, and four new stereogenic centers can be formed with almost complete control (eq 17). 3... 

The capnellenols, e.g. (24) [cf. (10)], are a unique family of sesquiterpenes, found in the soft coral Capnella imbricata. They are related structurally to the hirsutane family of triquinane terpenes, e.g. (18), but with the three methyl groups distributed differently about the tricycle. A special feature of the capnellenols is the presence of an unusual Wj-allylic alcohol functionality associated with ring c. The 8-epimer of (24) has now been synthesized by a route (Scheme 3) in which this novel functionality is introduced by annulation to (23) via reductive cyclization of the keto-acetylene precursor (22), followed by treatment of the resulting allylic alcohol (23) with t-butyl hydroperoxide in the presence of catalytic selenium dioxide. ... 

An analysis of the 2D-INADEQUATE NMR data performed by Yamada et al. for enriched Sc2 C66 fullerene has shown that this compound contains a C2v(4059)-C66 cage consisting of two sets of unsaturated linear triquinanes (ULTs), in which three pentagons abut one another and two scandium ions are located within the folds of each of the ULT units. Conclusive structural elucidation has been accomplished by single crystal XRD. 

Conformationally constrained triazacyclopenta[c]penta-lenes 128 are unprecedented tricyclic scaffolds and share the structural complexity characteristic of alkaloid natural products, such as triquinanes ° (e.g., 129 and 130), in that both scaffolds are composed entirely of fused five-membered rings and contain quaternary carbon centers (Figure 16.12). The triaza tricyclic ring system represents a source of chemical diversity that may complement traditional classes of heterocyclic compounds as potential pharmaceutical agents. 

Singh, V. and Alam, S.Q., Structural diversity through intramolecular cycloaddition and modulation of chemical reactivity in excited state. Synthesis and photoreactions of 3-oxa-tricy-clo[5.2.2.0 [ undecenones novel stereoselective route to oxa-triquinanes and oxa-sterpuranes,Bio-org. Med. Chem. Lett., 2517, 2000. 

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