Absolute configuration of CC-1065 by x-ray crystallography on a derivatized chiral fragment (CPI) from the natural antibiotic

Sequence selectivity of DNA covalent modification

“…for DNA sequences recognized by certain DNA binding proteins? Intriguingly, we have previously noted that the hierarchy of Spl binding sites in the 21 base pair repeats of SV40 DNA is predicted by the sequence selectivity of CC-1065 in this region of SV40 DNA (83,85). Second, if a conformational variant of DNA is entrapped by the covalent bonding of CC-1065, how does this affect DNA recognition by DNA binding proteins such as those involved in DNA repair or transcriptional control?…”

Synthesis, X-ray Structure, and Properties of Fluorocyclopropane Analogs of the Duocarmycins Incorporating the 9,9-Difluoro-1,2,9,9a-tetrahydrocyclopropa[c]benzo[e]indol-4-one (F2CBI) Alkylation Subunit

“…The structural effect of pulling the cyclopropane down is to impose stereoelectronic control on the ring opening reaction such that only the C8b−C9 bond is aligned for cleavage. This is nearly idealized with both the CBI and F 2 CBI nucleus and is less effectively accomplished with other subunits examined by X-ray to date including CPI, , DSA, and CBQ . Complementing this stereoelectronic control, the difluoro substitution of F 2 CBI may further stabilize a developing positive charge on C9.…”

Aryl Amidation Routes to Dihydropyrrolo[3,2-e]indoles and Pyrrolo[3,2-f]tetrahydroquinolines: Total Synthesis of the (±)-CC-1065 CPI Subunit

“…The western portion is referred to as the 1,2,8,8a-tetrahydrocyclopropa[c]pyrrolo[3,2- e ]indol-4-one, or CPI subunit for simplicity, and boasts an unprecedented and potentially reactive pyrrolo-fused cyclopropane which is bonded directly at C4 of the pyrrole and fused to a hexadienone moiety. The natural enantiomer of CC-1065 has the 8b R ,9a S stereochemical orientation of the cyclopropane ring in the CPI subunit (Figure ) 1 CC-1065 and related spirocyclopropyl dienone containing compounds.…”