Duocarmycin analogue

This inverse correlation has been noted in other instances of biological activity. The cytotoxic activity of a range of duocarmycin analogues behaved similarly. ... 

Carbenoid additions to y,y-difluoroallylic compounds represent valuable methodology complementary to the difluorocarbene chemistry described in Sect. 2.1. One example was provided by Boger and Jenkins [353] at Scripps during a synthesis of a duocarmycin analogue. Intramolecular rhodium-catalysed carbenoid addition of a p-quinonediazide to a protected difluoroallylic amine formed a key intermediate (Eq. 137). 

Scheme 37 Solid-phase synthesis of Duocarmycin analogues by Lown [25]...

Figure 12,3 Biologically active gem-difluorocyclopropane F2CBI as a duocarmycin analogue.

Travica S, Pors K, Loadman PM, Shnyder SD, Johansson I, Alandas MN, Sheldrake HM, Mkrtchian S, Patterson LH, Ingelman-Sundberg M (2013) Colon cancer-specific cytochrome P450 2W1 converts duocarmycin analogues into potent tumor cytotoxins. Clin Cancer Res 19 2952-2961... 

Asai, A. Nagamura, S. Saito, H. Takahashi, I. Nakano, H. The reversible DNA-alkylating activity of duocarmycin and its analogue. Nucleic Acids Res. 1994, 22, 88-93. 

Town [25] has reported a solid-phase radical cyclization approach to open-chain analogues of the cyclopropylindole class of antitumour antibiotics exemplified by duocarmycin SA (Fig. 1). 

A related cyclization was recently reported by Jia et al. [14] with allylamine 20 immobilized on poly styrene-Wang resin. The reaction was monitored by acetylation and cleavage to yield 21, as a mixture of free and Boc-protected amines. This solid-phase synthesis of. seco-CBI (21, R = H), related to the pharmacophore of the CC-1065 and duocarmycin class of cyclopropylindole antitumor antibiotics, has potential for the preparation of analogue libraries, and an example of further transformation of resin-bound 21 to a polyamide was presented. 

Tercel (99JOC5946) carried out a synthesis of the amino analogue 151 of the antitumour antibiotic duocarmycin SA, amino-seco-DSA (Scheme 38). 

Patel (97JOC8868) has used a 4-benzofuryl radical for the synthesis of seco-(-i-)-oxaduocarmycin SA (LY307918), an analogue of (-i-)-duocarmycin... 

In a tour de force over the next ten years, Natsume, Muratake, and colleagues applied their pyrrole-to-indole methodology to the syntheses of the trikentrins [10-13], pendohnycin [14], ( )- and (5)-pindolol [15], theherbindoles [13, 16], hapalindole O [17], mitosene analogues [18], and the duocarmycins [19, 20]. Several related companion... 

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