Tricyclic skeleton

Scheme 87 Synthesis of the tricyclic skeleton 443 of guanacastepene A (444) via diene-yne RCM [182]...

Thus, the dianion derived from a-amino acid substitutes the j8-chloride to give the ester of 2-(phenylsulfonyl)ethenyl amino acid and subsequent desulfonylation provides N-(benzoyl)vinylalanine methyl ester (62) (equation 61). The conjugate addition of enolates to methyl styryl sulfone (63) and subsequent intramolecular addition to the carbonyl moiety provide a synthetically valuable method for the construction of bicyclic and tricyclic skeletons . Desulfonylation of the cyclization product 64 with sodium in ethanol-THF gives the diene 65 in good yield (equation 62). 

A tandem Sakurai-carbonyl-ene sequence was used to create a tricyclic skeleton in the synthesis of a steroidal structure.50... 

A retrosynthetic analysis corresponding to the synthesis in Scheme 13.28 is given in Scheme 13.27. The striking feature of this synthesis is the structural simplicity of the key intermediate 27-IV. A synthesis according to this scheme generates the tricyclic skeleton in a single step from a monocyclic intermediate. The disconnection 27-III-27-IV corresponds to a cationic cyclization of the highly symmetric allylic cation 27-IVa. 

The synthesis in Scheme 13.29 also uses a remarkably simple starting material to achieve the construction of the tricyclic skeleton. A partial retrosynthesis is outlined below. 

Intermediate 29-1 contains the tricyclic skeleton of longifolene, shorn of its substituents, but containing carbonyl groups suitably placed so that the methyl groups at C(2) and C(6) and the C(11) methylene can be introduced. The retrosynthetic Step 29-1 =+ 29-11 corresponds to an intramolecular aldol addition. However, 29-11 is clearly strained relative to 29-1, and so (with OR = OH) should open to 29-1. 

A general synthesis of dibenzo-annelated dithieno[3,Z-b Z, 3 - thiophene 18 has been reported from bis(o-hydro-xyl)diacetylenes. This cyclization constructs a fused tricyclic skeleton in one pot. The subsequent dechalconization with copper powder produces a series of thiophene and selenophene-based heterocenes (Scheme 64) <20050L5301>. 

Fig. 52 Silver catalysed cyclisation in the synthesis of tricyclic skeleton of eunicin. 

In addition to the two asymmetric syntheses above described, two racemic syntheses of tetraponerines based on the 5=6-5 tricyclic skeleton have been published. Thus, Plehiers et al. [199] have reported a short and practical synthesis of ( )-decahydro-5Tf-dipyrrolo[l,2-a r,2/-c]pyrimidine-5-carbonitrile (238), a pivotal intermediate in the synthesis of racemic tetraponerines-1, -2, -5 and -6, in three steps and 24% overall yield from simple and inexpensive starting materials. The key reaction of the synthesis was a one-pot stereoselective multistep process, whereupon two molecules of A pyrroline react with diethylmalonate to afford the tricyclic lactam ester 239, possessing the 5-6-5 skeleton (Scheme 10). Hydrolysis of the carboethoxy group of 239 followed by decarboxylation yielded lactam 240, that was converted into a-aminonitrile 238 identical in all respects with the pivotal intermediate described by Yue et al. [200] in their tetraponerine synthesis. 

Isocupreidines are Cinchona alkaloid derivatives with limited conformational flexibility and increased basicity and nucleophilicity due to the increased ring strain of the tricyclic skeleton. The C(6 )-OH on (3-ICPD offers two different sites of simultaneous activation of nucleophile and electrophile to enhance basicity and sterics of intermediate species. 

MIRC and MIMIRC Reactions Leading to Spiropentanes, Tricyclo[3.2.1.0 ]octanes and Other Tricyclic Skeletons... 

The first successful synthesis of longifolene was described in detail by E. J. Corey and co-workers in 1964. Scheme 13.19 presents a retrosynthetic analysis corresponding to this route. A key disconnection is made on going from I => II. This transformation simplifies the tricyclic skeleton to a bicyclic one. For this disconnection to correspond to a reasonable synthetic step, the functionality in the intermediate to be cyclized must engender mutual reactivity between C-7 and C-10. This is achieved in diketone II, because an enolate generated by deprotonation at C-10 can undergo an intramolecular Michael addition to C-... 

Tricyclic skeletons such as 85, 87, 89 with a central benzene ring are formed in the fully intramolecular Pd-catalyzed cascade cyclization of 2-bromo-l-ene-//,w-diynes 84, 86, 88 and analogs (Scheme 24). This process involves two alkyne relays in a row and a final 67r-electrocyclization or 6-endo-trig carbopalladation with ensuing / -dehydropalladation. 

IPP and DMAPP lead to geranylpyrophosphate (GPP), which is an immediate precursor of monoterpenes. The formation of nerylpyrophosphate (NPP) from GPP gives rise to a wide range of acyclic, cyclic, bicyclic or tricyclic skeletons. Reactions like rearrangement, oxidation, reduction and hydration via various terpene cyclases result in the formation of numerous terpene derivatives. Condensation of GPP and IPP leads to farnesylpyrophosphate (FPP), the immediate precursor of sesquiterpenoids. Likewise, FPP and IPP are conducive to diterpenoids. 

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. 

Mitomycin A, 1, is a natural product which shows potent antibiotic and antitumor activity, and has been the subject of extensive synthetic studies. French workers have described a simple procedure for one-pot preparation of the tricyclic skeleton of the mitomycins. Thus, simply mixing and stirring a solution of nitrosobenzene and (E,E)-hexa-2,4-dienal in absolute ethanol at... 

These dianhydrohexoses constitute a complete series of eight isomers having rigid tricyclic skeletons, such as 3,8,9-trioxatricyclo[4.2.1.02 4]nonane and 3,7,9-trioxatricyclo[4.2.1.02 4]nonane, respectively, as represented here by l,6 2,3-dianhydro-4-deoxy- (131) and 1,6 3,4-dianhydro-2-dcoxy-/J-o-n o-hexopyranose (132). 

The zirconacycle 259 is prepared by the reaction of Cp2Zr with the 1,6-enyne 258, and converted to the cyclopentenone 260 by the reaction of CO. The silylalkyne 258 is the appropriate substrate, because the terminal alkyne can not be used in this reaction [111]. The tricyclic skeleton of tigliane 263 has been prepared by the carbonylative... 

As shown in template 91, a linker group can be attached to the tricyclic skeleton which results in the possibility to graft the template onto a solid support and synthesize template-bridged cyclic petide libraries using the split-and-mix method. 

The tricyclic skeleton of thieno[3,2-c][l,5]naphthyridine 9-7V-oxidc (263) was constructed (1993H245) in two ways by condensation of aldehyde 256 with pyridine /V-oxide 207 or (in lower yield) by the modified Suzuki reaction of the latter with 3-formylthiophene-2-boronic acid (264). 

The molecular structures of diazaphospholes and diazastiboles from X-ray diffraction studies are compiled in Tables 1 and 2. In every case, the five-membered ring is planar. In compound 10 (Equation 3) also, the tricyclic skeleton of its cation is planar. 

In the total synthesis of Danishefsky et al. (Figure 3) the tricyclic skeleton is established before the arabinosyl unit is linked [10]. The key steps of this synthesis are the Nozaki-Kishi cydization to the furanophane, a sequence of rearrangements to the 4,7-oxaeunicellane framework [11], and the oxycarbaglycosidation of the tricyclic core structure. 

Scheme 37 Preparation of [5.6.5]-tricyclic skeletons by cascade reactions on 2-bromo-dienynes [121-123]...

---