Pyrrolo tricyclic

A crystal structure is available for the compound with R = HC=C(CH2)2, and a mechanism was also proposed. On changing the reaction conditions (CH3CN, 82°C) and using Af-propionylimidazole, a tricyclic imidazo[l, 2 l,2]pyrrolo[2,3-6]furan was obtained in a diastereoselective spirocyclization reaction tl59],[157]... 

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]. 

Azomethine ylides of pyrrolo[l,2- ]pyrazine <1996JOC4655> and 3,4-dihydro pyrrolo[l,2-tf]pyrazine <1997T9341> undergo 1,3-dipolar cycloadditions with a number of dipolarophiles. For example, the ylide 178 reacts with propargylic ester 179 to give the tricyclic derivative 180 (Equation 43). 

An alternative strategy for the synthesis of these tricyclic compounds involves the reaction of the azidoalkenyl-functionalized furo[3,2-A]pyrrole 30, which reacts with triphenylphosphine to give the corresponding iminophos-phoranes 31 these upon reaction with aryl isocyanates give the pyrrolo[2, 3 4,5]furo[3,2-r-]pyridines 32, via the corresponding carbodiimides which are not isolated < 1994H(37) 1695, 1992M807> (Scheme 9). 

This class of tricyclic compound is dominated by the 377-pyrrolizines (systematically named 3//-pyrrolo[l,2- ]-pyrroles) and related systems, which are fused to another six-membered heterocyclic ring (Figure 1). 

Whereas Hegedus [335] and Danishefsky [336] were the first to discover a tandem Heck reaction from o-allyl-A -acryloylanilines leading to tricyclic pyrrolo[l,2-a]indoles or pyridino[l,2-a]indoles [336], it has been the fantastic work of Grigg to unleash the enormous potential of this chemistry. Grigg and his co-workers parlayed their Pd-catalyzed tandem polycyclization-anion capture sequence into a treasure trove of syntheses starting with IV-allyl-o-haloanilines [337-345], Diels-Alder and olefin metathesis reactions can be interwoven into the sequence or can serve as the culmination step, as can a wide variety of nucleophiles. An example of the transformation of 289 to 290 is shown below in which indole is the terminating nucleophile [340],... 

Some structures, related to pyrrolo[l,2- ]imidazoles, have been reported. The tricyclic perhydro derivative 49 <1997TL1647> as well as the 3-( 1 //-indol-3-ylmethy 1 )-7a-methyldihydro-1-phenylamino-l//-pyrrolo[ 1,2-tf] imidazole-2,5(3//,6//) dione 50 have been determined and some interesting aspects on compound 50 have been highlighted. 

Tryptophan and its derivatives can be characterized as existing in three possible tautomers the indole form, the indolenine form (hydrogen atom at position 3), and the cyclic form. In neutral solvents only the indole form exists NMR studies indicate no evidence for the other two isomers (60JA2184). However, when dissolved in 85% phosphoric acid or TFA, N-methoxycarbonyltryptophan exists as a pyrrolo[2,3-i]indole derivative 119 (78JA5564 81T1487). Although the tricyclic compound is stable in the crystalline form, it reverts to the starting material when it dissolves in acetic acid or methanolic HCl. 

From Lys hydrochloride pyrolyzed in vacuo at 600°C for 8-10 min, a tricyclic compound 134 is formed in low yield (80TL2679). Cystine reacts with dopachrome to give an unstable product, but the methyl ester of dopachrome gave a stable pyrrolo[2,3-/i][l,4]benzothiazine 135 (87T5357). 

Variation of the ring portion of acyclovir has been achieved. Compounds include monocyclic (isocytosine, triazole, imidazole), bicyclic (adenine, 8-azapurine, pyrrolo[2,3-c/]-pyrimidine, pyrazolo[3,4-[Pg.131]

A closely related reaction between 1 -arylpyrrolidine-2-thiones 96 and diethyl bromoma-lonate97 under Reformatsky conditions afforded l-arylpyrrolidin-2-ylidenemalonates 98, which, upon polyphosphoric acid (PPA) induced cyclization, opened a route to pyrrolo[l, 2-a] quinolones 99145, tricyclic analogues of quinolone antibiotics (equation 58). 

Another interesting synthetic route to pyrrolo[ 1,2-a]indoles is based on A-acetylindoxyl (92MC59). The reaction of A-acetylindoxyl with the diethyl acetal of dimethylformamide yielded enaminoketone (45), which subsequently gave a tricyclic enaminoketone (46) in an unexpected reaction... 

Fig. 7.13 Pyrido/imidazo/pyrrolo-puiinones as tricyclic xanthines with high affinity and potency at the hA3 AR subtype...

The C(2)-C(3) olefin of a l,4-benzodiazepin-5-one regiospecifically captured an alkyl radical intramolecularly in a 5-f vo-/r/g-proccss that is the critical step in an approach to the constmction of the fused tricyclic system found in the pyrrolo[2,l-f][l,4]benzodiazepine class of antitumor antibiotic. Treatment of the alkyl bromide 46 with Bu3SnH afforded the tricyclic product 47 in 90% yield, a reaction that proceeded with equal efficiency with the alkoxy aryl ring substituents found in the naturally occurring ( )DC-81 (Scheme 18) <19990L1835>. 

Electron densities obtained from molecular orbital calculations on thieno- and pyrrolo-fused derivatives are listed in Table XXIII (Part B). Similar values were obtained with furo- and isoxazolotropylium salts 218, 333, and 329 (Section III,B,2,b). In the field of tricyclic compounds, electron densities of furothieno-fused (237a, 238a) and bisthieno-fused ions (237b, 238b Scheme 57) were calculated (73ACS2257). 

A new route to 6-substituted pyrrolo[2,l-b]thiazoles 58 takes advantage of an intramolecular thermal cyclization of acetates 56 <07S3037>. These acetates are easily derived from the Morita-Baylis-Hillman adducts of thiazole-2-carboxaldehyde. This strategy has also been extended to the synthesis of the tricyclic analogs 60. 

Studies in the synthesis of the immunosuppressant FR901483 tricyclic skeleton showed that by palladium- and radical-mediated cyclizations of azaspiro-decanes the formation of azatricyclic derivatives was possible. Depending on the reaction conditions, 7,10 -methanopyrrolo[l,2- ]azocine 292 could be obtained from iV-(2-bromoprop-2-enyl)-l-azaspiro[4.5]decane 291 (Scheme 121) <2007ARKIVOG320>. When the reaction was performed in the presence of Bu3SnH, pyrrolo[2,3-r ]indoles were obtained instead. 

The carbodiimide mediated preparation of tricyclic pyrido[3, 2 4,5]pyrrolo[l,2-cjpyrimidine is a key step in the preparation of the marine alkaloid variolin... 

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