CC-1065/duocarmycin pharmacophore

Likewise, Sakamoto has synthesized the CC-1065/duocarmycin pharmacophore 284 via the cyclization of 282 [321]. Silver carbonate prevented unwanted isomerization of the exocyclic double bond in 283. Tietze and co-workers took full advantage of the power of these A-allyl-o-haloaniline Pd-catalyzed cyclizations in developing syntheses of the A-unit of CC-1065 and analogs [322-324]. 

Although not naturally occurring, benzene, furan, and thiophene analogs of CC-1065/duocarmycin pharmacophores (2-4) (Scheme 32) have been synthesized via Pd-catalyzed a-arylation, as briefly presented in Scheme 21. 

Sakamoto, T., Kondo, Y., Uchiyama, M. and Yamanaka, H. (1993) Concise s3mthesis of CC-1065/duocarmycin pharmacophore using the intramolecular Heck reaction. J. Chem. Soc., PerkinTrans. 1, 1941-2. 

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. 

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