Thio- and Seleno-nucleosides

3 -Thiothymidine and 2 -deoxy-3 -thioadenosine have been prepared by condensation methods. The vinyl sulfone 72 has been synthesized as a reactive 

Purine 2, 3 -dideoxy-4 -thio-L-nucleosides have been prepared by base-sugar condensation.  

The cyclopentene derivative 82 has been prepared from 2, 3 -0-isopropylidene-5 -thioadenosine, and was an irreversible inhibitor of S-adenosylmethionine decarboxylase.  

The sialic acid-cytidine conjugate 83 has been synthesized, the units being linked by displacement of a 5 -bromo-substituent on the nucleoside by a 2-thio-sialyl nucleophile.  

Reagents I. BteNBr, diglyme, 150 C ii, NH, III, sllylaled 5,ethyi ndlne. TmsOTI, HMDS 

The r-phenylselenyl derivative 73 was obtained, but with only low dia-stereoselectivity, by reaction of the enolate with PhSeCl. Treatment of 73 with NaBH4 in the presence of CeCh gave stereoselective reduction to alcohol 74.  

Reaction of a thiol with 5 -0-Dmtr-2,3 -anhydrothymidine was used to prepare S-(2-aminoethyl)-3 -thiothymidine, which was converted to its 5 -triphos-phate and coupled to an oxazine dye (see also ref. 67 above).  

5 -Acetylthio-2, 3 -0-isopropylideneadenosine has been made from iso-propylideneadenosine by a Mitsunobu reaction, giving a route to 5 -thioadenosine, and various S-alkylated derivatives such as the S-adenosyl-methionine analogues 90 (R = NH2, C02H).  

The nucleosides 91 have been prepared by coupling of the silylated bases with the methyl glycoside of the selenoanhydrofuranoside (Chapter 11), in the presence of TmsOTf.  

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A review has appeared dealing with the synthesis, chemical transformations and biological properties of thio- and seleno-nucleosides, with a section on C-sulfonate nucleosides and oligonucleotide analogues with sulfur-based linkages. ... 

The Pt bis chelates of some S- and Se-containing nucleosides or nucleotides have been synthesized and evaluated for antitumour activity in both in vitro and in vivo systems. The increased effectiveness of the trans chelate of selenoguanine is believed to be due to its slow dissociation and consequent release of the ligand into the blood stream. The delayed cytotoxicity observed for the Se compound was not obtained with the S analogue. The cw-diammineplatinum(II) 1 1 chelates of thio- and seleno-purines also have been prepared and evaluated against L1210 cells in mice. The Se chelate is active, with its stability affected by mouse serum, although the reason for the tatter is unclear. ... 

Viso A, Poopeiko N, Castilldn S (2000) Stereoselective synthesis of nucleosides from 1-thio and 1-seleno glycosides through consecutive 1,2-migration and glycosylation under Mitsunobu conditions. Tetrahedron Lett 41 407-411... 

The synthesis of purine and pyrimidine 2 -deoxynucleosides from a 1,2-dithio-sugar precursor is noted in Chapter 21, which also refers to the alkylation of seleno- and thio-substituted nucleosides using a mixture of a dialkyl disulphide (or diselenide) and tributylphosphine in DMF. Other thio-sugar derivatives are mentioned in Chapter 12. 

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