Antitumour agents, synthesis

Pyrimidine, 4-fluoro-2-isopropyl-synthesis, 3, 140 Pyrimidine, 4-fluoro-2-methoxy-synthesis, 3, 140 Pyrimidine, 4-fluoro-2-methyl-NMR, 3, 63 Pyrimidine, halo-aleoholysis, 3, 100 aminolysis, 3, 99 as antitumour agents, 3, 152 bipyrimidines from, 3, 103 Buseh biaryl synthesis, 3, 103 hydrolysis, 3, 101... 

H. Ouadid-Ahidouch, and J. M. Garcia Fernandez, Synthesis of N-, S-, and C-glycoside castanosper-mine analogues with selective neutral a-glucosidase inhibitory activity as antitumour agents, Chem. Commun., 46 (2010) 5328-5330. 

As part of the total synthesis of the triterpene (+)-a-onocerin, one of the first total syntheses in which RuO played a key role, a diphenylethyleneacetoxyketone was oxidised to the corresponding acetoxyketoacid by RuO /aq. Na(10yacetone. Aromatic ring oxidation was also involved (cf. 3.3.1 below) [219]. An oxidative cyclisation of a 1,5-diene to a diol by RuCl3/Na(10 )/wet SiO /THF formed part of the synthesis of the antitumour agent cw-solamin [220]. 

Synthesis of Analogues of Folic Acid, Aminopterin and Methotrexate as Antitumour Agents... 

The aldol reaction of dithioester enethiolates has been used for the synthesis of dithiolactones [123], chiral substrates for the Claisen rearrangement [124, 125], and oxathianes [126]. Thioamide enethiolates may be employed in this reaction as well as shown with /Tthiolactams [26], or with a precursor of the antitumour agent vinblastine [127]. 

The three bromine atoms of the tribromoimidazole 112 can be replaced sequentially in one pot, again in order of increasing basicity of the resulting organolithium." This method was applied to the synthesis of the antitumour agent carmethizole 113. 

Fredericamycin is a curious aromatic compound extracted in 1981 from the soil bacterium Streptomyces griseus. It is a powerful antibiotic and antitumour agent, and its structure is shown below. The first time it was made in the laboratory, in 1988, the chemists in Boston started their synthesis with three consecutive lithiation reactions two are ortholithiations, and the third is slightly different. You needn t be concerned about the reagents that react with the organolithiums just look at the lithiation reactions... 

One of the mildest methods for preparing methylene acetals involves reaction of a diol with dimethoxymethane in the presence of a suitable activating agent such as phosphorus pentoxide,176 trimethylsilyl Inflate.177 or lithium bromide and p-toluenesulfonic acid.178 The reaction is also used to make methoxymethyl ethers (see section 4.4,1) from alcohols. Scheme 3,95 illustrates the simultaneous formation of a methoxymethyl ether and a methylene acetal from Shikimic Acid.169 The reaction was adapted to the synthesis of the methylene acetal moiety of the marine antitumour agent Mycalamide B [Scheme 3.96],179... 

An excerpt of a synthesis of the potent antitumour agent FR-900482 [Scheme 3.126] illustrates the use of an N, O-acetal with additional Af-protection in the form of a 2,2,2-trichloroethoxycarbonyl (TVoc) group (see section 8.3.7) in a multifunctional environment.244 245 The A 0-acetal survived the mildly acidic conditions required to deprotect the p-methoxybenzyl group that preceded the formation of the triflate 1263. Later, reductive cleavage of the Troc group and simultaneous hydrolysis of the oxazolidine ring was accomplished in a single... 

During a synthesis of the marine antitumour agent Sarcodictyin A, selective removal of a secondary and a tertiary TES ether in the presence of a primary TIPS ether was effected by treatment with 5 equivalents of triethylamine trihy-drofluoride (Et3N 3HF)26 in THF at room temperature [Scheme 4,21 ].6... 

It should be noted that when the reaction is conducted with a chiral aldehyde and a chiral y-substituted allyltins, a matching effect when both partners impose a convergent selectivity, or a mismatching effect when the facial selectivity is divergent, may happen . Such a stereoconvergent effect was used in the synthesis of the antitumour agent azinomycin (equation 4). 

This chemistry is part of a synthesis of the antitumour agent vernolepin by S. Danishefsky and group, J. Am. Chem. Soc., 1976, 98, 3028,... 

Macrolides and Related Compounds. - Complex phosphonates continue to be used in the construction of carbon skeletons and in cyclisation reactions, as exemplified by the synthesis of didesepoxyrhizoxin, the biogenetic precursor of the antitumour agent rhizoxin, via intramolecular olefination of (225). (+)-Trienomycins A and F, members of a family of ansamycin antibiotics, have been synthesised using a double Wittig reaction of the diphosphonium salt (226) as a key step. The reaction produces a mixture of isomers including 21% of the required (all- ) product. 

The spectral properties and conformational preferences of some 1 jB -thiadiazole macrocycles have been reported. In connection with thiazoles we find mention of a useful reagent for the spectro-photometric determination of cobalt, 4C labelling of a new B-adrenergic blocking agent, S-596, and synthesis of analogues of the cationic terminus of the antitumour agent Bleomycin A21 . Additionally, a polymer-supported thiazolium salt catalyst, as a model for the thiamine-dependent enzymes, has been prepared, and three 2-alkylbenzothiazole volatile flavour constituents... 

Przybylski, E., Fell, E., Ringsdorf, H. and Zaharko, D.Z. (1978) Pharmacologically active polymers. 17. Synthesis and characterization of polymeric derivatives of the antitumour agent methotrexate. Makromol. Chem. 179 1719-1733. 

The drug exert its action due to its inherent antimitotic agent. It also inhibits protein synthesis. It is regarded to be the most active antitumour agent of the Amaryllidaceae alkaloids. 

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