Pyrrolo benzodiazepines

Reduction of all three of the double bonds in the pyrrolo-benzodiazepine-5,11-dione 105 with excess potassium provides the corresponding trans fused hexahydrobenzene derivative 106 in high yield with complete stereochemical control. The preparation of (+)-perhydro-219A 108 from 106 has been reported 3 and a general method of preparation of derivatives of /ra i-2-aminocyclohexanecarboxylic acid e.g. 107) has recently appeared. 

The precursor of (+ )-anthramycin, pyrrolo-benzodiazepine 196, can be synthesized by deprotection, acylation and reductive cyclization of pyrrolidine derivative 195, obtained by enyne metathesis (Scheme 40 (2004T9649)). 

Pyrrolo-benzodiazepine 199 with controlled stereochemistry has been prepared from the corresponding protected amino alcohol 198 in good yield (Scheme 41 (2003CC1688)). 

Tetrahydro pyrrolo-benzodiazepine 232 is a product of a two-step sequence starting from nitrile 231 (Scheme 49 (2005BMCL3453)). 

Direct acylation of imines 238 produces stable hydroxyl substituted pyrrolo-benzodiazepines 239 (Equation (29) (1993TL1929)). 

Pyrrolo-benzodiazepine dione 244 can be obtained from the ketoester 243 in refluxing AcOH in high yield (Scheme 52 (1991ZOR1951, 1992CE649, 1996PHA548, 2005H2451)). 

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. 

As with pyrrolo-benzodiazepine (1992JHC1005), 0x0 derivative of pyrrolo-benzothiadiazepine 203 (X = SO2) can be synthesized by the thermal cyclization of intermediate 205 (Scheme 42, Section 3.1.1.2 (1992SC1433)). 

Alkylation of pyrrolo-benzodiazepine dione 244 with methyl iodide occurs on both positions N9 and ClOa, while reaction with 2-bromo diethylaminoethane leads to the low yield of the 4-substituted 248. Acylations with benzoyl and 2-chloroacetyl chlorides are directed exclusively to position 4 to afford 247 (Scheme 52, Section 3.1.1.4 (1992CE649, 2005H2451)). Alkylation of 5H-benzo[/]-pyrrolo[l,2-d][l,4]diazepin-6(7H)-one with a substituted phenethyl bromide has been reported (Scheme 36, Section 3.1.1.1 (1992BMCL1639)). 

Reductive formylation of dihydro compounds derived from 4-arylmethyl pyrrolo-benzodiazepines 236 with formaldehyde in a Parr apparatus yields Af-methyl 237 (Scheme 50, Section 3.1.1.3 (1995EJM593)). 

Tetrahydro pyrrolo-benzodiazepine 232 can be oxidized with manganese (IV) oxide to imino analog 233 (Scheme 49, Section 3.1.1.3 (2005BMCL3453)). 

Di-carboxy substituted diazepine 226 results in spiro 228 after Boc-protection, hydrolysis, CDl activation and imide formation (Scheme 48, Section 3.1.1.3 (1993JHC897)). The conjugated ester group of (+ )-anthramycin derivative 197 can be constructed by cross-metathesis of pyrrolo-benzodiazepine 196 (Scheme 40, Section 3.1.1.2 (2004T9649)). 

Amino methyl substituted pyrrolo-benzodiazepine 215 forms a cyclic aminal with aldehydes that can be further oxidized with Mn02 to fused 3-substituted imidazole 216. Alternatively, cyclic imine 217 can be submitted to TosMlC cycli-zation to afford unsubstituted 9H-benzo[e]imidazo[5,l-c]pyrrolo[l,2-fl][l,4]-diazepine 218 (Scheme 45, Section 3.1.1.2 (1993JHC749)). 

Semiempirical molecular orbital calculations performed for a set of pyrrolo-benzodiazepines using MNDO and AMI were used for the interpretation of their mass-spectroscopic data (1996MI653). 

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

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>. 

Condensations of keto-esters (177) with o-phenylene-bis-methylamine afford the pyrido- and pyrrolo-benzodiazepines (178a) and (178b), although entry into... 

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