Pyrrolo benzodiazepines, formation

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)). 

Fusion of a 1,2,4-triazole ring to pyrrolo-benzodiazepine (1992JHC1005) and pyrrolo-benzothiadiazepine (1992SC1433) rings has been reported starting from 0X0 203 and included formation of the phosphonic imidate with formyl hydrazine (Scheme 42, Section 3.1.1.2). 

Reductive ring closure of l-(2-nitrobenzyl)-2-pyrrole carbaldehyde 200 results in pyrrolo[2,l-c][l,4]benzodiazepine 201 (Scheme 42 (1999BMCL1737)). On the other hand, oxo derivative 203 can be synthesized starting from aldehyde 200 through a nitrile formation/cyclizations multistep sequence. The alternate synthetic strategy included reduction of the intermediate acid (R = H) or ester (R = Et) 205 followed by CDI or thermal cyclization (1992JHC1005). 

Much work has been done on the photochemical ring-expansion of pyridine A -imides to 1,2-diazepines, but it has previously not proved possible to extend this reaction to the formation of 2,3-benzodiazepines (58) from isoquinoline A -imides (57). Now, however, it has been shown that this reaction can be effected in 30-50% yield if it is done in the presence of base. Full reports have now been published on the photolysis of thieno-, furo-, and pyrrolo-[ ]- and -[c]-pyridine A -imides. These reactions give both 1,2-and 1,3-diazepines fused to the heteroaromatic rings (see these Reports, Volumes 2 and 3). 

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