Kinamycin antibiotics

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

Keywords Alkylation Diazo Diazonium DNA cleavage Kinamycin antibiotics Lomaiviticin antibiotics... 

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]. 

Synthetic studies on kinamycin antibiotics in the laboratory of T. Ishikawa resulted in the elaboration of the highly oxygenated D ring with all the required stereocenters for the kinamycin skeletons.The tricyclic tertiary alcohol was converted to the corresponding xanthate and then smoothly pyrolyzed under reduced pressure to yield the desired tetrahydrofluorenone system. 

Kumamoto, T., Tabe, N., Yamaguchi, K., Yagishita, H., iwasa, H., ishikawa, T. Synthetic studies on kinamycin antibiotics eiaboration of a highiy oxygenated D ring. Tetrahedron 2001, 57, 2717-2728. 

Origin of Cyanamide Carbon of Kinamycin Antibiotics. J. Amer. Chem. Soc. 

Cone, M. C. Seaton, R J. Halley, K. A. Gould, S. J. New products related to kinamycin from Streptomyces murayamaensis. I. Taxonomy, production, isolation and biological properties. J. Antibiot. 1989, 42, 179-188. 

Porco s synthesis of ( )-kinamycin C (3) constituted the first reported route to any of the diazofluorene antitumor antibiotics. This synthesis invokes several powerful transformations, including a modified Baylis-Hillman reaction, a catalyst-controlled asymmetric nucleophilic epoxidation, and a regioselective epoxide opening to establish the D-ring of the kinamycins. The tetracyclic skeleton was constructed by an... 

Kinamycin and Lomaiviticin Antibiotics Importance of Diazo Group. . . 140... 

Abstract Diazonium salts have been previously used to cleave DNA via generation of carbon centered radicals and cations. Efforts have been made in the past decade or so to develop diazo compounds and a-diazoketones for physiologically relevant DNA cleavage. These efforts, coupled with their relevance to the mechanism of action of kinamycin and lomaiviticin antibiotics and other naturally occurring diazo compounds, will be discussed. 

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 presence of 9-diazofluorene groups in kinamycin antitumor natural products would lead one to think of an active role for the diazo group. The hypothesis may be substantiated by the fact that one of the precursors in kinamycin biosynthesis, kinafluorenone 10 [44], which lacks the diazo moiety, shows no antibiotic activity against B. subtilis ATCC 6633, known to be very sensitive to the kinamycins. However, prekinamycin (9) [49], which is similar to kinafluorenone but retains the diazo group, shows activity to-... 

Table 13. Novel kinamycin benzo [b] fluorene antibiotics, biosynthesized via the angucyclinone dehydrorabelomycin (257)...

The enantioselective total synthesis of the diazobenzofiuorene antibiotic (-)-kinamycin C (91) via the coupling of bromoenone 88 with naphthylstannane 89, has been reported by Porco and coworkers... 

Intramolecular or partially intramolecular cycloaddition reactions are extremely useful tools in the synthesis of polycyclic molecules, since they can allow the construction of several rings in a single step. Preliminary studies indicate that this general principle also holds for partially intramolecular versions of the palladium-catalyzed cocycloaddition of arynes and alkynes. For example, benzo[fc]fluorenones 144a-d, which constitute the polycyclic skeleton of the kinamycin family of antitumour antibiotics, can be obtained by [2+2+2] cy-... 

The kinamycins (6), antibiotics produced by Streptomyces murayamaensis, are composed of a partially reduced carbazole nucleus.A purple compound isolated in small quantities from the same species is believed to have the structure 7 on basis of spectroscopic data. Compounds similar to 7 are proposed as biosynthetic precursors of the kinamycins. 3 ... 

Methods for the synthesis of tetracyclic benzocarbazoles and benzo-b-carbazoloquinone have become relevant to alkaloidal synthesis due to the progress in the chemistry of the kinamycin group antibiotics. 

Cone, M.C., P.J. Seaton, K.A. Halles, and S.J. Gould New Products Related to Kinamycin from Streptomyces murrayamaensis Taxonomy, Production, Isolation and Biological Properties. J. Antibiotics 42, 179 (1989). 

---