Tricyclic framework

Fig. 31 Synthesis of a tricyclic framework using ene-yne metathesis and Diels-Alder reaction. 

Synthesis of a sugar derived allene and its intramolecular silver mediated etherification followed by ring closing metathesis has been explored for building the tricyclic framework of eunicin (Fig. 52).68... 

The following sections give an overview of the total syntheses of kelsoene that have been reported by other groups. With respect to the key step by which the tricyclic framework is constituted, they can be divided into two groups, the [2-1-2]-photocycloaddition approach and the homo-Favorskii strategy. 

In contrast to the [2-1-2]-photocycloaddition which is a widely used method to generate four-membered rings, Koreeda and Zhang used a thermal rearrangement key step to construct the tricyclic framework of kelsoene [23]. In earlier work, it was shown that upon treatment with base, y-keto-p-toluene-sulfonate rac-32 is converted to a 44/56 mixture of bicyclo[3.1.1 ]heptanone rac-33 and bicyclo[3.2.0]heptanone rac-34 (Scheme 10) [24-26]. 

The importance of the rigid tricyclic framework for the formation and stability of the cyclol has been examined by the Italian group. Cyclization of a similar tripeptide derivative containing cysteine as N-terminal residue... 

Addition of a cyanohydrin acetal anion to [(benzene)Cr(CO)3] followed by reaction with allyl bromide produces the cyclohexadiene derivative (73) in 94% yield, which undergoes a Diels-Alder reaction rapidly to give a tricyclic framework (74). After quenching with methyl iodide and disassembling of the cyanohydrin group, the diketone (75) is obtained in 50% yield overall (equation 51).125 These products are obviously interesting as potential intermediates for synthesis. 

In addition to the stereochemical structure of the tricyclic skeleton, the conformation of the amino-substituted side chain can influence the psychotropic activity of such compounds. According to the theory of Wilhelm, transmission of the basic psychotropic activity depends largely on the constellation adopted by the side chain. However, the main psychotropic action (neuroleptic or thymoleptic) is chiefly a function of the particular stereochemistry of the tricyclic framework. 

Although reactions at ring heteroatoms have been conducted and reported on members of this class of heterocycles, in general the outcome of these is not reflective of a unique characteristic of the tricyclic framework. 

As illustrated in Equation (1), a Lewis acid-promoted intramolecular conjugate addition of a furan to a dienone was used to generate the seven-membered ring of the fused tricyclic framework of sesquiterpene echinofuran <2003T1877>. The use of Et2AlCl provided the best result, minimizing undesired polymerization of the furan substrate 3. 

In the related tricyclic framework of the two epimeric silphiperfolcncs 7 agreement with reported isolated yields169 is almost perfect in both epimers three conformers contribute to the favored and four conformers to the disfavored mode of attack. 

The potential of sequential radical addition as a powerful method to achieve the formation of five-membered rings was fully realized in the tandem radical cyclization strategy devised by Curran for the synthesis of triquinanes. In the case of linearly fused triquinanes, such as hirsutene 90 (Scheme 3.40), this strategy implies the retrosynthetic disconnection of the tricyclic framework by the application of two sequential radical cyclization transforms at rings A and... 

The enantioselective total synthesis of the cyclooctanoid natural product (+)-epoxydictymene was accomplished in the laboratory of L.A. Paquette. The entire tricyclic framework was constructed by the application of a Claisen rerrangement via a chairlike transition state. The precursor for this / 3,37-sigmatropic rearrangement was obtained by treating a lactone precursor with the solution of the Tebbe reagent in the presence of pyridine. The corresponding enol ether was formed in almost quantitative yield, and immediately after isolation it was treated with triisobutylaluminum to effect the Claisen rearrangement. 

Intramolecular meta photocycloaddition of 2-MeC6H4CH2CMe2CH2CH CH2 provides appropriate tetracyclic precursors from which the key tricyclic framework required for the synthesis of ( )-ceratopicanol can be obtained.This constitutes an example of a typical holosynthon. N-Benzoyl-N-benzylcinnama-mides and related compounds will photocycloadd in the presence of benzil to give 3-azatricyclo[5.2.2.0 ]undeca-8,10-dien-4-ones with high stereoselectivity, and this constitutes the first example of a photochemical [4+2] cycloaddition of an enone to a benzene ring. For example, irradiation of (60 R = H, alkyl, phenyl = H, Me X = H, OMe, Cl, etc.) gives (61 same R, R, X). 

The specific feature of peri-annulation consists in the fact that the extraction of a heteromonocycle is impossible. Therefore, the minimum structural unit in this case is the tricyclic framework, for instance, (VII-IX). It is therefore obvious that peri-annulated heterocyclic systems possess qualitatively new structural features sufficient to separate these substances into an independent domain distinct from the array of the heteromonocyclic and ortho-fused heterocycles. 

Given the desired 5-HT4/5-HT3 receptor profile and pharmacological efficacy of SC-52491, a scalable synthesis was developed. The aza-noradamantane ring system found in this agent possesses four contiguous chiral centers within its tricyclic framework. An asymmetric route was deemed to be superior to resolution of racemates, as previous efforts along the latter pathway resulted in difficult separations of fairly end-stage intermediates [22]. 

BusSnH/AIBN to give the desired tricyclic framework 97 and 98 in moderate and good yields, respectively <04L2855>. 

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