Pyrrolo benzodiazepine synthesis

Pyrrolo[2,1 -c][l, 4]benzodiazepines synthesis, 7, 614 Pyrrolo[l, 6]benzodiazocines synthesis, 7, 515 Pyrrolo[3,4-c]benzopyrazoles reactions, 6, 1034 Pyrrolobenzothiazoles synthesis, 4, 785 Pyrrolo[l, 2-c]benzotriazines synthesis, 4, 240 Pyrrolo[3,4-c]cinnolines synthesis, 4, 240... 

Similar to pyrrolo-benzodiazepines, pyrrolo-benzotriazepines 225 (X = NMe) with a spiro piperidine moiety have been reported (Scheme 47, Section 3.1.1.3 (1992JHC241)). Their synthesis included direct reaction of hydrazine 224 (X = NMe) with N-substituted 4-piperidones to afford 225 in 42-63% yields. 

ASYMMETRIC SYNTHESIS OF TRANS-2-AMINOCYCLOHEXANECARBOXYLIC ACID DERIVATIVES FROM PYRROLO BENZODIAZEPINE-5,11 -DIONES... 

Pyrrolo[ 1,4] benzodiazepines, synthesis and action on central nervous system (CNS) 8OYGK11O5,... 

Kamal has extended the azide reduction/DlBAL-H methodology to the synthesis of C2-azido analogues of the pyrrolo-benzodiazepine derivatives 107 and 108 <04TL3499>. 

The carbinolamine-containing pyrrolo[2,l-c][l,4]benzodiazepine family of antitumor antibiotics is produced by various Streptomyces species well-known members include abthramy-cine, tomay mycine, and DC-81,138 Various approaches to the synthesis of these compounds have been investigated over past years reductive cyclization of suitably substituted nitroaldehydes is the frequently used method (Eq. 10.81).139... 

A concise synthesis of the novel pyrrolo[l,2-a]benzodiazepine system 92, using the metallocarben-oid/spiro-[6,5]-ammoniumylide/Stevens[l,2]-shift with ring-expansion approach, was reported. The overall cascade process was stereospecific <07T12232>. 

Pyranonaphthoquinone antibiotics, total synthesis of 86YGK918. Pyrrolo[ 1,4] benzodiazepine antibiotics, biosynthesis of 80ACR263, d,/-Saxitoxin, total synthesis of 80/7(14)1477. 

Singh, R., Jain, P.C., and Anand, N., Potential anticancer agents. Synthesis of some substituted pyrrolo[2,l-c][l,4]benzodiazepines, Indian J. Chem., Sect. B, 21B. 225. 1982. 

Diastereoselective intramolecular 1,3-dipolar cycloaddition reactions were deftly exploited in the synthesis of a number of enantiopure pyrazolo-pyrrolo- and triazolo-pyrrolo-fused 1,4-benzodiazepine systems <05S2246>. 

An efficient route to the synthesis of the cytotoxic pyrrolo[2,l-c][l,4]benzodiazepines 97-99 with conjugated C2-acrylyl substituents based on a Heck coupling of 96 to introduce this C2 side-chain. The route started from the nitro benzoic acid 93, and proceeded via standard transformations to 94, which was then cyclised to the 7-membered ring derivative 95 on oxidation of the primary alcohol to the aldehyde <04BMCL1547>. 

Kamal and co-workers have reported a new approach for the solid-phase synthesis of the pyrrolo[2,l-c][l,4]benzodiazepines 102 using a thiol Wang resin. The interesting feature of this approach was the reductive cleavage and cyclization achieved in the last step on reaction with DIBAL-H yields of the products 102 ranged from 57% (R = 7-OMe, 8-OBn) to 65% (R = H) <04TL7667>. 

This reaction principle has considerable scope, as shown by the synthesis of various heterocyclic annu-lated 1,4-benzodiazepines. [l,2,3]Triazolo[l,5-fl][l,4]benzodiazepines 23 are prepared from triazole derivatives 22 which are accessible by a 1,3-dipolar cycloaddition of o-azidobenzophenones with (aminomethyl)alkines pyrrolo[2,l-c][l,4]benzodiazepines 25 are formed from l,2-dihydro-3,l-benzoxazinediones 24 and proline ... 

Quite recently, it has been shown that reduction of nitro and azido arenes to N-arylformamides using ZnHC02NH4 under microwave conditions proceeds well. In the absence of irradiation the reaction leads to amines. This interesting procedure was extended to the synthesis of 4-(3H)-quinozolinones and pyrrolo[2,l-c][l,4]benzodiazepines [213]. 

There is an increasing interest in the synthesis of fused diazepines with potential anti-tumour activity. A new direct synthesis of pyrrolo[2,l-c][l,4]-benzodiazepin-5-ones, e.g. (105), has been developed en route to a complete synthesis of the anti-tumour antibiotic sibiromycin. Two routes have been devised to the novel pyrrolo[l,2- f][l,4]benzodiazepin-6-one system, but members of this series were inactive as sedative, depressive, or myorelaxant agents. ... 

Kamal, A. Shankaraiah, N. Devaiah, V. Reddy, K.L. An efficient solid-phase synthesis of biologically important DNA-interactive pyrrolo[2,l-c][l,4]benzodiazepine dimers (DSB-120) and their C2-fluorinated analogues. Tetrahedron Lett. 2006, 47, 6553-6556. 

Reduction of Azides to Amines. In situ generated TMSI has been found to be a useful reducing agent for the reduction of azides to amines (eq 56). The reaction is carried out under extremely mild and neutral conditions, and a number of aryl, alkyl, and aroyl azides are suitable for this tranformation. This methodology has also been applied to the synthesis of pyrrolo[2,1-c][l,4]benzodiazepines via reductive cyclization of w-azido carbonyl corrqtounds. ... 

This methodology with some variations has been utilized in the synthesis of numerous heterocyclic systems, such as heterocycle-fused quinolinone derivatives [391], l,4-benzodiazepin-2-ones [392], benzo-, naphtho- and heterocycle-fused pyrrolo[2,l-c][l,4]diazepines [393], quinolinone or pyrrolidinone derivatives [394], dibenzo[fl,c]phenanthridines [395], thiazolo-fused quinolinones [396], isoindolinone and isoquinolin-2-one derivatives [397], indoline derivatives [398], 5-aroyl-pyrrolidinones [399,400], indazolone derivatives [401,402], substituted indolizidinones [403], 1-arylpyrrolopyrazinones [404], stmcturally diverse... 

Giiesbeck AG, Kramer W, Lex J (2001) Diastereo- and enantioselective synthesis if pyrrolo [l,4]benzodiazepines through decarboxylative photocyclization. Angew Chem Int Ed 40 577-579... 

Kamal A, Devaiah V, Reddy K, Kumar M (2005) Synthesis and biological activity of fluoroquinolone-pyrrolo[2,l-c][l,4]benzodiazepine conjugates. Biooig Med Chem 13 2021-2029... 

The iV-oxides not only of quinoxalines but also of 1,4-benzodiazepines can serve as excellent 1,3-dipoles in the synthesis of derivatives of pyrrolo[l,2-fl]quinoxa-lines. For example, the reaction of chlorodiazepineoxide 133 with dimethyl acetylenedicarboxylate takes place by a scheme of 1,3-dipolar addition with the... 

A special method for the synthesis of pyrrolo[l,2-a]quinoxalines using the PA4 synthon has not been developed. However, during the production of pyrrolo-1,4-benzodiazepines by the insertion of carbon monoxide into 2-[N-R-N-(2-bromophenyl)aminomethyl]pyrrolidines 187 in the presence of catalytic amounts of Pd(OAc)2 and PPhs pyrrolo[l,2-a]quinoxalines 190 were found together with other products formed as a result of the migration of, for example, an acyl group from the aniline nitrogen atom to the pyrrolidine nitrogen atom (Scheme 3.56) (Mory et al. 1984). 

Mory M, Purvaneckas GE, Shikura M, Ban Y (1984) New synthesis of pyrrolo-1, 4-benzodiazepines by utilizing palladium-catalyzed carbonylation. Chem Phann Bull 32 (10) 3840-3847. doi 10.1248/cpb.32.3840... 

Figure 13.30 Biocatalytic azide reduction-cyclization sequence for the synthesis of various pyrrolo[2,l-c][l,4]benzodiazepines, potential antitumor antibiotics.

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