Multicyclic compounds

Figure 15.3. Examples of complex multicyclic compounds that can be separated and identified by GC-MS.

Figure 11.3 Molecular structure of the multicyclic compounds cubane, tetrahydrodicyclopenta-diene and adamantane...

Products F and G were in turn substrates for subsequent pairing reactions to obtain multicyclic compounds J, N, K, O, and H. Finally, products B, J, and H, which all comprise a diene functionality could be further converted by a subsequent Diels-Alder (DA) reaction with 4-methyl-l,2,4-triazolin-3,5-dione to obtain the highly complex products I, M, and L. This example shows that by applying the build/couple/pair strategy a collection of 15 highly diverse (and complex) scaffolds can be obtained in only three to five steps. ... 

The pyrrole ring appears in some pharmaceuticals, but multicyclic compounds, especially based on indole, are of more common occurrence. Pyrrolidines also are of importance. An application of the Paal-Knorr method in the pharmaceutical field is found in the synthesis of clopirac, which is a nonsteroidal anti-inflammatory dmg (a group of agents known as NSAlDs). The starting material (Scheme 9.5) is hexane-2,5-dione (actually introduced as the diketal 2,5-dimethoxytetrahydrofuran, which hydrolyzes to the diketone). 

ALICYCLIC COMPOUNDS Adamantane derivatives Other multicyclic compounds Monocyclic compounds... 

Intramolecular cyclopropanation was useful for the construction of multicyclic compounds in a diastereoselective manner. The carbene species in 137 attacked the aromatic double bond to give fused cyclopropane 138 in good yield [110]. The obtained cyclopropane 138 underwent irrevCTsible ring cleavage to give naphthopyranes (Scheme 1.66). 

Intramolecular cyclopropanations catalyzed by Cu-BOX catalysts have been frequently used for the synthesis of multicyclic compounds. For example, Nakada and coworkers examined intramolecular cyclopropanation to prepare... 

Using the sequence of Cu(l)-catalyzed photocycloaddition of diallyl ethers or homoallyl vinyl ethers and RUO4 oxidation, a variety of novel multicyclic compounds such as 86 and 89 can be synthesized (Scheme 23) starting with the dienes 84 and 87, respectively. 

Thus, the comprehensive investigations above demonstrate that a variety of multicyclic compounds with quaternary stereogenic centres can be obtained from this class of dien-ynes, depending on the length of the tethering chain as well as on the substituents of the unsaturated functions. The efficiency of cationic Tol-BEM-AP/Rhodium complexes as catalysts for many reactions of this class has been assessed. 

Shibata T, Tahara Y, Tamura K, Endo K (2008) Enantioselective syntheses of various chiral multicyclic compounds with quaternary carbon stereocenters by catalytic intramolecular cycloaddition. J Am Chem Soc 130 3451-3457... 

In the same manner we succeeded in the formation of multicyclic nonskid-chain-like polyaza compounds with an increasing number of macrocyclic chains per iteration step [17] (Fig. 5). 

The same authors also combined the [2+2+1] cycloaddihon with a Diels-Alder reaction [281]. For this multicyclization, the dienediyne 6/4-18 was treated with 5 mol% C02(C0)8 under 30 atm CO at 130 °C for 18 h to give the tetracyclic compound 6/4-19 (Scheme 6/4.6). 

Intramolecular versions of the Heck reaction are very useful for the construction of ring systems. The entropic advantage of having both coupling partners present in the same molecule increases the efficiency of the insertion reaction and leads to efficient reactions. Moreover the intramolecular version can be carried out on hindered substituted alkenes, whereas the intermolecular Heck reaction is largely restricted to monosubstituted alkenes. These reactions illustrate the syn stereochemistry of both the insertion reaction and the elimination. A number of multicyclic natural products have been synthesized using intramolecular Heck reactions to assemble the skeletons, and this has become a powerful synthetic tool for such compounds. 

Because of the presence of the cyclic four-membered amide connected to the multicyclic ring systems, an effort to define their mechanism of action would be highly important. Despite a number of synthetic efforts, a relatively small amount of research had been focused on the use of compounds related to PAHs as anticancer agents. Bair et al. [152, 153] reported a close correlation between antitumor activity and the shape of the polyaromatic system. However, his group did not make a definitive correlation between the ability of these compounds to bind to deoxyribonucleic acid (DNA) and their cytotoxic activity. Bair s group developed... 

Chavan and coworkers provide evidence that the Wolff rearrangement is facilitated by the formation of silver nanoclusters, which initiate electron transfer to the diazo compound providing 8. While the precise fate of this species remains to be firmly established, they suggest a multicycle process involving the intermediacy of a silver carbene 10 (Scheme 8.2).10 12 Decomposition of the silver carbene to the free carbene 14 precedes rearrangement to ketene 13, which is then trapped with water to provide the carboxylic acid 15 (Scheme 8.2). 

Compounds with opioid activity are structurally diverse, ranging from rigid multicyclic... 

Osapay G, Taylor JW (1992) Multicyclic polypeptide model compounds.2. Synthesis and conformational properties of a highly a-helical uncosapeptide constrained by 3 side-chain to side-chain lactam bridges. J Am Chem Soc 114 6966-6973... 

It was early recognized <72CC1242,74JCS(P1)1694> that carbenes, generated from diazo compounds, added to phosphorus to produce the ylide structure. 1,2,5-Triphenylphosphole has been the usual participant in this reaction (Schemes 42 and 43). When some multicyclic diazo compounds were... 

As example one may consider the observed anionic tetrahedron complexes of the four normal valence compounds with the same classification code °8/3, shown in Figure 13. The first three tetrahedron complexes are constructed alone of < 8/3 base tetrahedra. In Na2Ge2Se5 and Na2Ge2S5 the base tetrahedra are only comer linked, however in Rb4ln2Sg comer and edge linked. Even if there are only comer linked base tetrahedra the anionic tetrahedron complex may have the shape of a two-dimensional layer or a cyclic molecule. Rnally, the anionic tetrahedron complex in Cs4Ge Se5, a multicyclic molecule, is constructed, instead of 8/3 base tetrahedra, of °8/2 and 8/4 base tetrahedra in equal proportions. 

Enantioselective intermolecular [2-F2-F2] cycloadditions of 1,6-diynes with a,fS-unsaturated carbonyl compounds are valuable methods for the synthesis of chiral cyclohexadienes in a single step [36]. The intramolecular Diels-Alder reaction (IMDA) is known to be a powerful strategy for the construction of complex multicyclic skeletons [37]. Tanaka reported an efficient enantioselective domino intermolecular [2-F2-F2]/IMDA cycioaddition reaction occurring between 1,6-diyne 106 and amide-linked 1,5-diene 107 bearing two sterically and/or electronically... 

Terpenes are hydrocarbon compounds through the condensation of several isoprene units. Terpenoids, in fact, are modified terpenes, wherein some methyl groups have been removed or replaced, often oxygen atoms added. Most of them are multicyclic structures which differ from one another not only in their basic carlxMi skeletons but also in functional groups. The structural unit of terpenoid building blocks is isopentenyl pyrophosphate (IPP). 

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