Tricyclic core

Bromo-A -tosylindole (8) has been converted to arcyriacyanin A (9) by Steglich. Similarly, Rapapport used 3,4-dibromoindole (10) to construct the ergot alkaloid tricyclic core (11), and Murakami reported a relatively short route to costaclavine." Similar uses in other natural product syntheses continue to appear in the literature. ... 

Scheme 8.51 Construction of the tricyclic core of phomactin A through a retroaldol reaction.

A similar synthetic strategy was applied in the synthesis of menogaril 83, another important anthracycline antitumour antibiotic, and to the synthesis of the tricyclic core of olivin 87, the aglycon of the antitumour antibiotic olivomycin [61,62]. In both cases a tandem benzannulation/Friedel-Crafts cyclisation sequence yielded the tetracyclic and tricyclic carbon core, respectively (Scheme 42). 

It should be also noted that, in a very recent publication, Liu and coworkers were successful in applying microwave radiation within their domino approach towards the synthesis of pyrrolo[2,l-fc]quinazoline alkaloids such as deoxyvasicinone, 8-hy-droxydeoxyvasicinone, mackinazolinone and isaindigotone, which exhibit a promising broad spectrum of biological activities. In the case of isaindigotone, the authors were able to extend their strategy to a three-component procedure, which comprises the domino conversion of anthranilic acids and Boc-protected amino acids into the tricyclic core skeleton [43]. 

Balzarini and co-workers utilized a sodium hydride-mediated condensation of the aminopurininone 230 with N-(4-bromoacetylphenyl)-isobutyramide 231 in dimethylformamide to give the tricyclic core ring system 232 in low yield (Equation 63) <2002JME5052>. 

An elegant approach toward formation of the central tetrahydropyrimidine ring has been reported by Tamura and co-workers who utilized an aza-Diels-Alder cyclization of ethyl ( )-3-aza-3-(l,3-benzoxazol-2-yl)propenoate 266 with a range of cinnamyl alcohols 267 catalyzed by l,l,3,3-tetra- -butyl-l,3-diisothiocyanatodistannoxane, and subsequent lactonization to generate the tricyclic core structure 268 (Scheme 18) <1998J(P1)3389>. 

The tricyclic core of spirotryprostatin B can be formed via formation of the dihydropyrrole 325 <2000AGE4596>. Removal of the silyl protecting group of 322, followed by Dess-Martin oxidation, and reaction of the resultant aldehyde with the potassium salt of the diketopiperazine phosphonate 323 led to formation of the enamide 324. 

The ring system 413 is an intermediate in the synthesis of the tricyclic core of the marine alkaloids sarains A-C (Scheme 32) <1998JOC8096>. 

Synthesis of a tricyclic core of marine alkaloid variolin B has been achieved in three steps. The key reaction involves tandem deoxygenation and cylization of a triarylmethanol 187 using a combination of trifluoroacetic acid (TFA) and triethylsilane (TES). The use of 4.3equiv of TFA and 8.1 equiv of TES minimizes the formation of side products 188, 189 and allows the formation of the desired product 190 in 34% yield (Scheme 5) <2005JOC6204>. 

Lastly, Livinghouse s approach to the tricyclic core of 4 is highlighted by an acylnitrilium spirocyclization [19d], Exposure of isonitrile 48 to thiophenyl acetyl chloride provides an intermediate chloramine (49) that, in the presence of a silver salt, eliminates the chloride to form a nitrilium ion (R-N = C+-R). The nitrilium is attacked by the nucleophilic aromatic ring to furnish spirocyclic imine 50 in high... 

Several examples reported in 2006 demonstrate that 2-substituted furans underwent spirocyclization at the 2-position. As illustrated in the scheme below, the reaction of a furan tethered at the 2-position to an iminium ion gave a spiro-2,5-dihydrofuran derivative as the sole diastereoisomer. This spirocyclization, which proceeded irrespective of the length of the carbon linker, was employed to construct the ABC tricyclic core of manzamine A <06OL27>. 

A novel tricyclic piperidine-fused pyrazolo[l,5-a]pyrimidin-7-(4//)-one has been synthesized with regioselective formation of the tricyclic core structure <06MI715>. 

Lindsay and Pyne utilized microwave heating for a base-catalyzed cleavage of the oxazolodinone group during the total synthesis of the tricyclic core structure of the cromine alkaloids (Scheme 6.160 b) [263]. 

As will be discussed later, the novel pentacyclic antitumor alkaloid roseophilin continues to attract much synthetic effort and several approaches relied on the venerable Paal-Knorr condensation for construction of the pyrrole moiety. For instance, Trost utilized this reaction upon diketone 1 to afford the tricyclic core 2 of roseophilin in a strategy featuring an enyne metathesis as a key step <00JA3801>, while another formal synthesis of this alkaloid utilized a radical macrocyclization to produce the ketopyrrole core <00JCS(P1)3389>. 

The metal-catalyzed [5 + 2]-cycloaddition of tethered VCPs and 7r-systems has been applied to the total syntheses of (-l-)-dictamnol,52 (+)-aphanomol l,53 and tremulenolide A.54 The tricyclic core of cyathane diterpenes such as (-l-)-allocyathin B25S and the tricyclic carbon skeleton of polyhydroazulenes such as dolatriol56 were also synthesized... 

Similar to the Pd-catalyzed pyrrole and thiophene annulations, an intramolecular Heck reaction of substrate 91 resulted in benzofuran 92 [80], Such an approach has become a popular means of synthesizing fused furans. Muratake et al. exploited the intramolecular Heck cyclization to establish the tricyclic core structure en route to the synthesis of a furan analog of duocarmycin SA, a potent cytotoxic antibiotic [81]. Under Jeffery s phase-transfer catalysis conditions, substrate 93 was converted to tricyclic derivatives 94 and 95 as an inseparable mixture (ca. 4 1) of two double bond isomers. 

Seike H, Sorensen EJ (2008) A synthesis of the tricyclic core structure of FR901483 featuring an Ugi four-component coupling and a remarkably selective elimination reaction. 

Before an asymmetric synthesis appeared of levofloxacin (1, (—)-ofloxacin), (—)- ofloxacin was isolated via optical, enzymatic, and crystallization resolution of the racemic ofloxacin (17) Drugs Future, 1992 Hayakawa et al., 1986, 1991). For instance, tricyclic core 52 was converted to ( + )-3,5-dinitrobenzoyl derivative 54 in 75% yield (Scheme 4.5). The enantiomers were then separated via high-performance liquid chromatography (HPLC) with a SUMIPAX OA-4200 column to deliver optically pure benzoyl esters 55a and 55b (Drugs Future, 1992 Hayakawa et al., 1986, 1991). 

A double reduction was achieved under catalytic hydrogenation conditions to open the epoxide and reduce the nitro group to an amino group in 90% yield. The aniline thus afforded was reacted with diethylethoxymethylenemalonate to give 92. 92 was next cyclized to the 1,4-benzoxazine 93 via a Mitsunobu reaction in the absence of a Lewis acid, unlike Kim s approach (Kang et al., 1996). Completion of the tricycle core was ultimately achieved in PPE at 140-145°C to furnish the LVX core in 85% yield. The core was converted to LVX (1) in two precedented steps. 

Langlois and co-workers have developed a Bradsher cycloaddition route, involving a [2,7]naphthyridinium salt toward the tricyclic core of manzamine A (Scheme 71) <1995TL9475, 1998TL837, 2000TL9251>. 

The tricyclic core of duocarmycin has been produced by a novel copper-mediated aryl amination reaction, which cleanly gives the cyclized product under exceptionally mild conditions <2003JA6630>. Selective /) tw-bromination of indoline with T-bromosuccinimide (NBS) in DMF followed by aryl amination using 2 equiv of copper iodide quantitatively provides the indolinone (Equation 71). 

Several reports for the synthesis of coumarins have used lactone formation to erect the tricyclic core (Equation 44) < 1995T3197,1999SC929>. Other approaches to similar coumarins include the ring opening of an epoxide (Equation 45) <2002TA1799>. 

The marine alkaloid sarain A 383 features an exceptionally challenging pentacyclic architecture (Figure 6). To date, 383 has not succumbed to a total synthesis. Two groups however have completed the tricyclic core of 383 and have annulated the western 13-membered ring using quite similar RCM approaches. " The results obtained with... 

A synthesis of the highly functionalized tricyclic core of guanacasterpene represents an example of the Rh(i)-catalyzed intramolecular PKR leading to bicyclo[5,3,0]-decanes from the allenynes (Equation (50)). ... 

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