Enantioselective Total Synthesis of (+)-Duocarmycin A, epi-(+)-Duocarmycin A, and Their Unnatural Enantiomers

Design and Synthesis of Dynemicin Analogs

“…Examples Interestingly, this compound already contains an aromatic are the mitosenes, [1] the cyclopropyl ring containing ring. In this case reductive activation is needed to cleave the CC-1065, [2,3] duocarmycin, [3,4] and certain anthracyc-NϪO bond. [10] CC-1065 and duocarmycin, on the other linones.…”

“…Reduction of It is clear that with the modular structure dynemicin A and the other enediynes are suitable lead compounds for the amide was accomplished after formation of the quinolyl triflate followed by treatment with formic acid and a catadevelopment of less toxic analogs. As in the anthracyclines [11c] [18] the aromatic part provides room for ample modi-lytic amount of Pd(PPh 3 ) 4 . The enediyne was attached in one step to the quinoline 10.…”

Synthesis and evaluation of duocarmycin SA analogs incorporating the methyl 1,2,8,8a-tetrahydrocyclopropa[c]imidazolo[4,5-e]indol-4-one-6-carboxylate (CImI) alkylation subunit

“…4 The study of the natural products, 5-8 their synthetic unnatural enantiomers, 9 and key analogs 10 has defined structural features that control their DNA alkylation selectivity, 4,10 efficiency, rate, reversibility, 11 and catalysis, 12 providing a detailed understanding of the relationships between structure, reactivity, and biological activity. 13 Central to these studies have been modifications in the DNA alkylation subunit of the natural products and the establishment of the impact that the deep-seated changes have on their functional reactivity and biological properties.…”

“…Thus, the compounds are ordinarily unreactive, but are activated for adenine N3 alkylation upon target DNA binding. 13,23 Moreover, this reactivity is still attenuated, 9 allowing selective reaction by appropriately positioned adenines within the preferred AT-rich non-covalent binding sites such that it is the non-covalent binding selectivity of the compounds that controls the alkylation site selectivity. 24 It was not apparent how the substitution of the fused imidazole of CImI for the pyrrole would impact this key structural feature of the natural products.…”

Synthesis of Indolin‐3‐ones and Tetrahydro‐4‐quinolones from α‐Imino Esters

“…[3f] Ethylation of the imino nitrogen atoms gave the intermediate aluminum enolates, which added to the methoxycarbonyl or cyano moieties to give the indolin-3-one 5 or its imino derivative 7 a, [11] respectively, in good yields. For the formation of the acetylimino derivative 7, chloro-, methoxy-, and methyl-substituted analogues also gave good yields of the products (Table 5, entries 2-4).…”