Boronic nucleoside derivatives

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. 

An improved synthesis of 1,2-0-cyclohexylidene-myo-inositol in 45 -50% yield utilized the reaction of 1,1-dimethoxycyclohexane with myoinositol in DMSO catalyzed by Nafion-H, a perfluorinated strongly acidic ion exchange resin. Minor products were the 1,2 3 4- 1 2 4,5- and 1,2 5t6-diacetals. The acidic reagent systems, phosphorus pentoxide-trimethylsilyl triflate and phosphorus pent-oxide-boron trifluoride etherate, have proved effective for 0-methoxymethylation of carbohydrate and nucleoside derivatives with dimethoxymethane noteworthy is the compatibility of the reagents... 

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. 

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. 

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. 

Many 6-alkylaminopurine nucleosides are important adenosine receptor antagonists, and acyclic nucleotide analogues derived from 6-dialkylaminopurines are strong antivirals, anti-neoplastic agents, and immunomodulators. Recently, several 6-(arylalkynyl)-, 6-(arylalkenyl)-, and 6-(arylalkyl)purines have been reported to exhibit cytokinine activity. Suzuki crosscoupling reactions of 9-benzyl-6-chloropurine with boronic acids have recently been reported to provide 6-substituted purines in moderate to excellent yields (Eq. (46)) [77]. 

From the known, differential complexing between boronic acids and polyhydroxy compounds, it follows that carbohydrate mixtures may be separated by column-chromatographic methods that exploit the differences. Nucleoside and nucleotide boronates have been separated on columns of anion-exchange resins,90 and sugars and alditols have been shown to be differentially retained on such resins in the sulfonated phenylboronic acid form,64 but perhaps the best uses of column chromatography in this connection have incorporated the resolving powers of insoluble polymers to which boronic acid groups have been covalently bonded. Such insoluble forms of boronates have been synthesized either by substitution of polysaccharide derivatives, or by polymerization of suitable arylboronic acids. 

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... 

Alternatively, the construction of these nucleosides was achieved from the alkoxyamine derivative 520 by conversion to the respective formamidine 519. Transamidination followed by boron-trifluoride-catalyzed cyclization gave the imidazoles 522. Their cyclization was effected using sodium methyl-... 

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