Boron-containing nucleoside

Boron-containing nucleosides, carboranyl-substituted nucleotides, porphyrins, and boron analogs of acridine in neutron-capture therapy 04IZV1795. 

Palladium-catalyzed coupling between halogenated nucleosides and ar-ylstannanes containing a boronic acid substituent (see below) in the aryl group proceeds chemoselectively at the C—Sn bond rather than at the C—B bond to give boron-containing nucleosides (166). The methodology... 

Barth, R. E., W. Yang, A. S. al Madhoun, J. Johnsamuel, Y. Byun, S. Chandra, D. R. Smith, W. Tjarks, and S. Eriksson. 2004. Boron-containing nucleosides as potential delivery agents for neutron capture therapy of brain tumors. Cancer Res. 64 6287-6295. 

Boron-containing nucleosides are considered as promising candidates for BNCT because of their potential to be retained in rapidly dividing tumor cells after 5 -monophosphorylation by phosphory-lating enzymes, thymidine kinase 1 and deoxycytidine kinase. Thymidine kinase 1 is pyrimidine... 

Synthesis of a number of boron-containing nucleosides prepared by reaction of the 1,4-dioxane derivative of cobalt bisfdicarbollide) with the canonical nucleosides thymidine, 2 -D-deoxycytidine, 2 -0-deoxyadenosine, and 2 -0-deoxyguanosine has been described. Direct reaction of the oxo-nium cycle opening results in a mixture of O- and Af-boronated nucleosides that were separated by chromatography [58,59]. Syntheses of ferra bis(dicarbollide)-based [59] and do50-dodecaborate-based [60] nucleosides were reported as well. Structures of some of these nucleosides are shown in Figure 9.7. 

The azide derivatives described were successfully applied for the synthesis of boron-containing nucleosides (Figure 24.12) [55-57] and porphyrins (Figure 24.13) [58] using click chemistry methods. 

A series of boron-containing nucleosides was prepared by the reactions of the 1,4-dioxane derivative of cobalt bis(dicarbollide) with the canonical nucleosides—thymidine, 2 -0-deoxycytidine, 2 -0-deoxyadenosine, and 2 -0-deoxyguanosine (Figure 24.17). In the case of thymidine and 2 -0-deoxyguanosine the reactions result in mixtures of theN- and 0-alkylated products, which can be separated by chromatographic methods [73,74]. The 2 -0-deoxyadenosine derivatives of iron and cromium bis(dicarbollides) were prepared in a similar way [75,76]. 

Recently, Brown has shown the feasibility of a one-carbon homologation procedure using a chiral non-racemic boronate derived from the hydroboration of 3-pyrroline. Pyrrole-containing nucleosides have been prepared from the pyrroline nucleoside by photodehydrogenation.9... 

Dihydroxyboryl)-2 -deoxyuridine and some related boron-containing pyrimidines had been synthesized for use in BNCT (Schinazi and Prusoff 1985). As for b-5-o-carboranyl-2 -deoxyuridine, it is a nontoxic pyrimidine nucleoside analog designed for BNCT of brain tumors (Schinazi et al. 2000). 

De Clercq has reviewed the antiviral activity spectrum as related to the target of action for different classes of nucleoside analogues, and the potential of boron-containing pyrimidines, nucleosides and oligonucleotides in neutron-capture therapy has been discussed. A memorial tribute to the life and work of R.K. Robins has been given, along with a bibliography of Robins publications. ... 

Boron-containing analogs of the biochemical precursors of nucleic acids, including purines, pyrimidines, thymines, nucleosides, and nucleotides, have been synthesized and several were evaluated in cellular and animal studies. Figure 10.8 shows several representative molecules of this class (35-42) containing carborane cages linked via various spacers to either the base or the carbohydrate... 

Yamamoto, Y, Seko, T., and Nemoto, H. 1989. New method for the synthesis of boron-10 containing nucleoside derivatives for neutron-capture therapy via palladium-catalyzed reaction. J. Org. Chem. 54 4734-4736. 

Sephadex and 0-(2-diethylaminoethyl)cellulose with a-bromotolyl-boronic acid, and studied the separation of free sugars92,93 and nucleosides and nucleotides93,94 on them at various pH values and with different eluants. Compounds containing cis-1,2-diol groupings were, again, the most strongly bound. 

In numerous synthetic studies it has been demonstrated that DMP can be used for a selective oxidation of alcohols containing sensitive functional groups, such as unsaturated alcohols [297,1215-1218], carbohydrates and polyhydroxy derivatives [1216, 1219-1221], silyl ethers [1222,1223], amines and amides [1224-1227], various nucleoside derivatives [1228-1231], selenides [1232], tellurides [1233], phosphine oxides [1234], homoallylic and homopropargylic alcohols [1235], fluoroalcohols [1236-1239] and boronate esters [1240]. Several representative examples of these oxidations are shown below in Schemes 3.349-3.354. Specifically, the functionalized allylic alcohols 870, the Baylis-Hillman adducts of aryl aldehydes and alkyl acrylates, are efficiently oxidized with DMP to the corresponding a-methylene-p-keto esters 871 (Scheme 3.349) [1217]. The attempted Swern oxidation of the same adducts 870 resulted in substitution of the allylic hydroxyl group by chloride. 

Column Chromatography — A model has been developed that closely predicts the elution of salt and sucrose during preparative chromatography on Na -form cation-exchange resin. It required minor adjustment for application to beet molasses due to an induced change in the resin from Na - to K -form, but was less accurate when the load of molasses containing 32% w/v dry matter was increased beyond 10% of bed volume. The binding of nucleosides and nucleotides to boronate affinity columns at pH 7 was enhanced by fluoride ion (and to some extent chloride ion) in the eluant, due to the formation of tetravalent fluoroboronate species. As a consequence, an improved separation of adenosine from 2 -deoxyadenosine was achieved. ... 

A detailed stndy of the combination of flnorescein boronic acid with diol-appended quenchers a-c and comparison with the fluorescence outputs of nonboron or nondiol-containing systems (i.e., fluorescein or methyl red were employed directly) revealed that the boronate ester formation results in enhanced quenching in each case, and that compound c is the best overall quencher. Nncle-osides were also shown to bind to the same fluorescein boronic acid derivative. While the quenching ability of each nucleoside tested was different, the same ratiometric quenching enhancement was observed in each case, sng-gesting similar binding affinities. 

Boronate affinity has gained increasing attention as a unique means for the selective capture and separation of ris-diol-containing biomolecules in recent years. " Since the use of boronate affinity for the separation of carbohydrates and nucleic acid components was reported by Weith and co-workers in 1970, boronate affinity has been used for the separation of various ds-di-ol-containing compounds, including nucleosides, nucleotides, nucleic acids, catechols, carbohydrates and glycoproteins. 

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