5-Diazobenzo fluorene

FIGURE 7.23 Prototype diazobenzo[6]fluorene-based natural products kinamycin A and prekinamycin. Compounds prepared for this study are shown in the inset. 

Figure 7.23 shows the prototype diazobenzo[Z ]fluorene-based natural products kinamycin A and prekinamycin. The kinamycin A-D family were first isolated from Streptomyces murayamaensis, but the structures were incorrectly characterized as having a cyanobenzo[Z ]carbazole ring. Since the initial discovery of the kinamycins, many new analogues have been discovered from natural sources.88-92... 

Kinamycin Antibiotics Revised Structures as Diazobenzo[b]fluorenes. . 137... 

A series of publications elucidating the correct structure of kinamycins A, B, C, and D as 5-diazobenzo[fr]fluorenes (7a-f, Fig. 13), have appeared in the literature [41,42], The earlier assignment of these antibiotics as benzolfr]carbazoloquinonccynamides [40] (Fig. 14) was discarded upon mismatch of the synthesized structure with the natural products. While most of them are known to possess antibacterial activity, some have shown considerable toxicity to cancerous cells [44,46,47]. 

The isolation of diazobenzo[fr ]fluorenes as stable antitumor natural products raises several questions about their mode of action. The inability to cleave DNA by diazotization of 9-aminofluorene may imply that if the diazo functionality is involved in the mode of interaction of kinamycins with DNA, its conversion to diazonium and the ensuing reduction may seem to be of negligible importance. An additional possibility, which will be discussed later, is that 9-diazofluorene may not be the ideal model for these natural products. In exploring DNA cleavage as a possible route to the kinamycins role as a stable antitumor agent, which may supplement their speculative and as yet unconfirmed role as alkylating molecules [67], this early model seemed to suggest that the well-established activation of diazonium may not be relevant. 

The structures of the kinamycins were revised recently [177, 178], as they were shown to be 5-diazobenzo[h]fluorenes, e.g. 256 (kinamycin D), and not cyanocarbazoles as originally designated. The biosynthetic relation of the kinamycin antibiotics to the angucycline group was established by biosynthetic studies revealing dehydrorabelomycin (257) as their biosynthetic intermediate (Scheme 56) [3,179]. 

---