Antitumour antibiotics

A similar synthetic strategy was applied in the synthesis of menogaril 83, another important anthracycline antitumour antibiotic, and to the synthesis of the tricyclic core of olivin 87, the aglycon of the antitumour antibiotic olivomycin [61,62]. In both cases a tandem benzannulation/Friedel-Crafts cyclisation sequence yielded the tetracyclic and tricyclic carbon core, respectively (Scheme 42). 

Intensive studies towards the total synthesis of fredericamycin A 91 culminated in the enantioselective synthesis of this potent antitumour antibiotic [63]. 

Furopyrrolizidine, antitumour antibiotic 46 can be brominated by reacting with NBS in TF1F at rt to give the 7-bromo derivative 229 in 64% yield. The reaction can be reversed by refluxing 229 with dimedone in toluene to give back 46 in 80% yield. Compound 229 on further reaction with diethylamine in toluene afforded thermodynamically more stable epimer 231 (Scheme 37) <2002OL4387>. 

Roe, S.M., Prodromou, C., O Brien, R., Ladbury, J.E., Piper, P.W. and Pearl, L.H. (1999) Structural basis for inhibition of the Hsp90 molecular chaperone by the antitumour antibiotics radicicol and geldanamycin. Journal of Medicinal Chemistry, 42, 260-266. 

An enediyne antitumour antibiotic, namenamicin (185) was isolated from Polysyncraton lithostrotum from Fiji [176]. 

The allylic radical (124) has been characterized by ESR as an intermediate in the photolysis of the deoxyribose phosphate (122), a model system for DNA cleavage by antitumour antibiotics (Scheme 18).282 The proposed mechanistic pathway follows that... 

During synthetic studies on the antitumour antibiotic CC-1065, ready access was required to a series of 6-substituted indole-3-carboxylates. The following example illustrates the successful general strategy that was developed reaction of the N-Cbz derivative of N-(3-methylphenyl)hydroxylamine with methyl propiolate in nitromethane as solvent and in the presence of Hunig s base gave methyl l-benzyloxycarbonyl-6-methylindole-3-carboxylate directly in 89% yield. 

Lown JW (1993) Discovery and development of anthracycline antitumour antibiotics. Chem Soc Rev 22, 165-176. 

Echinosporin (XK-213) is a novel antitumour antibiotic isolated1 from the fermentation broths of Streptomyces echinosporus. It is of great pharmacological interest on account of its significant anticancer effects in several rodent tumour models. (—)-Echinosporin was recently synthesised in enantiomerically pure form by A.B. Smith and coworkers starting from L-ascorbic acid.2 Their synthesis is described below. 

Bleomycin, an antitumour antibiotic, binds iron in the reduced, divalent state to its secondary amide group. It binds low molecular weight iron ions (often loosely referred to as free iron) in forms that catalyse free radical reactions (Gutteridge et al., 1981) but not iron bound within native, functional protein structures, such as ferritin, transferrin, lactoferrin, haemoglobin, myoglobin, cytochromes etc. The resulting bleomycin-iron complex is capable of degrading DNA... 

In the final step of a synthesis of the antitumour antibiotic Lankacidin C, Kende and co-workers55 were faced with the difficult deprotection of a bis-TBS ether [Scheme 4.35] without cleavage of the delicate pyrandione ring. Desilylation failed with all variants of fluoride or HF, but it was finally achieved using aqueous formic acid at 20 °C for 3 h to produce Lankacidin C in 82% yield. 

The extremely broad functional group tolerance of the Pd-catalysed N-de protection of Aloe groups was a crucial design feature in a synthesis of the epoxy-quinol core of the Manumycin family of antitumour antibiotics [Scheme 8,80].195 Note the convenient generation of the Pd(0) catalyst in situ from reaction of dichlorobis(triphenylphosphine)palladium(II) with tributylstannane. The use of sodium borohydride and borane dime thy lamine complex is illustrated in Schemes 8.81193 and 8.82194 respectively. 

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). 

Oxidation of the lithium enolate of 1-tetralone 23 to (—)-2-hydroxy-l-tetralone 24, the AB ring synthon of the antitumour antibiotic rhodomycinones, with (+)-18 (X = OMe, Y = H, equation 10) resulted in much better enantiomeric excess values (ee >94%) than hydroxylation with other oxaridines. ... 

Last year Rawal and Cava gave a preliminary account of their studies into the photocyclization of 1,2-dipyrrolyl-ethylenes and related systems and pointed out that such photo-oxidative cyclization may be employed as the key step to the tricyclic ring structure present in the antitumour antibiotic dipeptide CC-1065t The same workers have reported further on the photochemistry of... 

Another incorrect structure was revealed by synthetic work aimed at structure 44, alleged to be a part structure (the chromophore ) of the antitumour antibiotic kedarcidin. The synthesis was successful but revealed that the structure was wrong as the compound is a P-amino acid and not an a-amino acid as had been assumed.6... 

Catalytic debenzylation of the ketoamide (29.8) is accompanied by cyclization and, if desired, the hydroxylactam produced may be dehydrated to the 2-methylene derivative (29.9, R = CHj) (which is a degradation product of auro-momycin, an antitumour antibiotic) in 94% yield by treatment with methane-sulphonyl chIoride-JV,iV-di-isopropylethylamine. 

Intramolecular olefination of the phosphonates (184) and (186) has been used as the final step in syntheses of (+j-jolkinolides (e.g. 185)108 and the antitumour, antibiotic asperlin (187),109 respectively. In the latter case this confirms the stereochemistry of asperlin as (65,7/ ). A new synthesis of ( )-a,p-unsaturated macrocyclic lactones by intramolecular Wittig reaction of [Pg.356]

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