Tricyclic subunit

The cycloadduct of indane and vinyl acetate (136) has also figured in a clever synthesis of decarboxy-quadrone (145 Scheme 19) reported by Mehta. For this target the cycloadduct is reduced and solvol-yzed to provide alcohol (142). Dimethylation and rearrangement provides the required tricyclic subunit of the target. 

The first total synthesis of the marine polycyclic ether toxin (-)-gambierol was accomplished in the laboratory of M. Sasaki. The introduction of the a,(3-unsaturation into the seven-membered H ring of the FGH tricyclic subunit proved to be problematic, because both the conventional selenium-based method and the Nicolaou oxidation with IBX failed. However, when the seven-membered ketone was treated with LiHMDS in the presence of TMSCI and EtsN, the corresponding silyl enol ether was formed, which was oxidized under Saegusa conditions to give the desired cyclic enone in high yield. Because of the small scale of the reaction, a large excess of Pd(OAc)2 was used in acetonitrile so the presence of a co-oxidant was not necessary. 

To build the central ABC core present in 1, two main synthetic strategies have been used Diels-Alder reactions and asymmetric synthesis. This tricyclic subunit was chosen as the first synthetic target because it contains all five stereogenic carbons. A central pyrrolo-isoquinoline skeleton (ABC) was initially synthesized by the high-pressure Diels-Alder reaction of 3-alkyl-5,6-dihydro-2-pyridones with Danishefsky s diene, followed by deprotection and spontaneous pyrrolidine ring closure (see Scheme 16) [77]. 

Jamison and coworkers developed a bromonium-initiated polyepoxide-opening cascade in their total synthesis of mt-dioxepandehydrothyrsiferol ( /if-40) (Scheme 4.8) [16]. Treatment of trisepoxide 38 with A -bromosuccinimide (NBS) in HFIP resulted in the formation of a 7,7,6-trans-anti-trans-fused tricyclic subunit 39a and 39b in 72% yield as a mixture of two diastereomers (dr = 1 1). All the quaternary stereocenters in 38 (C6, CIO, and C15) underwent clean inversion to afford the desired trans-anti-trans geometry of ring junctions in 39a and 39b. 

The importance of the 1,3-dipolar cycloaddition reaction for the synthesis of five-membered heterocycles arises from the many possible dipole/dipolarophile combinations. Five-membered heterocycles are often found as structural subunits of natural products. Furthermore an intramolecular variant makes possible the formation of more complex structures from relatively simple starting materials. For example the tricyclic compound 10 is formed from 9 by an intramolecular cycloaddition in 80% yield ... 

The Pschorr reaction also works with substrates containing a bridge other than oxygen. Thus various tricyclic products containing a biaryl subunit are accessible, e.g. carbazoles and fluorenes. 

Multiple drugs (PPIs, prokinet- G-protein Pj-subunit (GNP3) 825C>T ics, spasmolytics, tricyclic antidepressants)... 

De Meijere, StaUce and coworkers were able to generate dilithiated 111, where the tricyclic non-metalated form can be considered as a subunit of the smallest possible fullerene By a two-fold tin-lithium exchange of the bis(trimethylstanno) derivative 110 with methyllithium, the dilithium compound 111 was cleanly obtained (Scheme 39) its solid-state structure could be clarified by means of X-ray crystallography. 

If one of the C —C double bonds of the 1,6-diene is incorporated in or attached to a ring (e.g., cycloalkene, methylenecycloalkane) tricyclic compounds containing a bicyclo[3.2.0]heptane subunit are obtained as products. Thus, photobicyclization of monocyclic diallyl ethers or homoallyl vinyl ethers afford oxatricycloalkanes.6 Similarly, allylic alcohols containing an additional cycloalkenyl ring are converted to oxatricycloalkanes by irradiation in the presence of copper(I) trifluoromethanesulfonate as catalyst.9... 

A pentacyclic diterpene 1 called dictyoxetane contains a most unusual subunit, a 2,7-dioxatricyclo[4.2.1.03>8 ]nonane. During model studies designed to provide access to this key subunit the bicyclic ether 2 was synthesised in the hope that Sn displacement would generate the unsaturated tricyclic oxetane. There was no reaction when 2 was treated with base. Reaction with a catalytic amount of p-toluenesulfonic acid in DMF at 75°C for 24 hours resulted only in formation of 4-methylacetophenone. The hydroxy mesylate 2 is also reported to decompose to 4-methylacetophenone on storage. 

Reaction of functionalized bicyclic compound with DDQ provided the tricyclic core of phomactin A. This product with a dihydrofuran subunit, was extremely unstable and dehydrated readily to form the corresponding furan <02OL2413>. 

On account of their very important biological activity, /9-lactams are important synthetic targets [4-9]. Fused polycyclic -lactam subunits appear in many natural products such as penicillins [4-6] and trinems/tribac-tams [10-13]. Fu et al. reported that such frameworks can be prepared with high levels of enantioselectivity via the intramolecular Kinugasa reaction [ 14, 15] of alkyne-nitrone in the presence of a planar chiral Cu/phosphaferrocene-oxazoline catalyst [16]. For instance, compound 1 was transformed into tricyclic /9-lactam 3 in good stereoselectivity and yielded (88% ee and 74% yield) using 5 mol % of CuBr and 5.5 mol % of complex 2 (Scheme 1). 

It has been demonstrated that cycloadducts (129), which are enolphosphates obtained by regio- and stereospecific [4 + 2] cycloaddition reactions of dienes (130) to a variety of dienophiles, are functionalized versatile synthons having fixed stereochemistry. Their [2,3] sigmatropic rearrangement via allylic sulfoxides and selenoxides (131) provides a direct sterospecific entry to new functionalized bi- and tricyclic allylic alcohol systems (133). The latter has been transformed into the corresponding a-hydroxy ketones (132), key structural subunits of natural products and valuable synthetic intermediates (examples are given in Scheme 32). ... 

The enzyme is also subject to allosteric inhibition. When glucose binds at the active site, it stabiles the T-state conformation of the enzyme. The T state is also stabilised by bi- or tricyclic aromatic compounds such as caffeine or flavins, which bind at the entrance to the active site tunnel,and by acylated p-glucopyranosylamine derivatives, which bind similarly to glucose, but more tightly. A third allosteric site, formed at the interface of two subunits and normally an internal pool of water molecules , has recently been discovered in rabbit muscle phosphorylase b " and human liver phosphorylase a. Occupancy of this site freezes the enzyme in the T state and inhibitors with 10 M dissociation constants from the site are being investigated in the treatment of diabetes. 

Among the many isolated sesquiterpene lactones, the nonisoprenoid hydroazulenic pseudogua-ianolides are the largest family51. Most of these tricyclic compounds contain a c -fused /3-lactone subunit, as well as a trans-fused hydroazulene. In a synthesis of damsin. a./i-unsatu-rated lactone 5 was hydrogenated over platinum on carbon to yield an 85 15 mixture of the C-6-isomeric products 6 with a <7s-fused lactone subunit49. 

Construction of the Tricyclic ABC Ring Subunit of Manzamine A via a Novel Intramolecular Diels-Alder Reaction. Martin, S. F. Rein, T. and Liao, Y. Tetrahedron Lett. 1991, 32, 6481. 

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