5983-11-9

Upstream product

• 56822-33-4 3',5'-di-O-mesylthymidine 
• 139419-06-0 (R)-1-(5-methylene-2-tetrahydrofuranyl)thymine 
• 52523-38-3 (R)-1-(2,5-dihydro-5-methylene-2-furanyl)-5-methyl-2,4(1H,3H)-pyrimidinedione 
• 155807-21-9 1-(3,5-anhydro-2-deoxy-β-D-threo-pentofuranosyl)-2-O-ethylthymine 

Relevant academic research and scientific papers

Electrophile-promoted addition of hydroxymethylphosphonate to 4′,5′-didehydronucleosides: a way to novel isosteric analogues of 5′-nucleotides

An electrophile-promoted addition of dialkyl-hydroxymethylphosphonate to the protected 4′,5′-didehydronucleosides resulted in an epimeric mixture of 4′-dialkylphosphonomethoxy derivatives of 2′,5′-dideoxynucleosides, novel analogues of 2′-deoxynucleoside 5′-monophosphates. Several types of electrophiles (pyridinium tosylate, NIS, NBS, MCPBA and others) were evaluated in addition reactions with 4′,5′-didehydrothymidine. Out of them, pyridinium tosylate was found to have a practical usefulness in these transformations. Its use has led to the preparation of a series of 4′-phosphonomethoxy derivatives of common 2′-deoxynucleosides. On biological screening, these free phosphonic acids exerted no significant cytostatic or antiviral activity.

Synthesis of Some 2',3'-Didehydro-2',3'-didepxynucleosodes Derived from Modified Pyrimidine Bases

3',5'-Bis-O-(4-tolylsulfonyl)-thymidine and 2'-deoxyuridine (13a and 13b) reacted with sodium ethoxide in boiling ethanol to give the corresponding ethoxy-oxetanes 12a and 12b in 67 and 66percent overal yield for the two-step processes starting from thymidine 4a and 2'-deoxyuridine 4b, respectively.Treatment of the ethoxy-oxetanes 12a and 12b with hydrogen sulfide and N1,N1,N3,N3-tetramethylguanidine in dry pyridine solution gave the 2-thiothymine- and 2-thiouracyl-derived oxetanes 19a and 19b in 62 and 68.5percent yield, respectively.When the latter compounds were treated with potassium tert-butoxide in dimethyl sulfoxide, the corresponding 2',3'-didehydro-2',3'-dideoxynucleosides (d4 nucleosides) 10a and 10b were obtained in 66 and 60percent yield, respectively.The 2-thiothymine-derived oxetane 19a was converted via the 5-methyl-2-thiocytosine-derived oxetane 21a into the 5-methyl-2-thiocytosine-derived d4 nucleoside 11a in 59.5percent overall yield; the 2-thiouracil-derived oxetane 19b was similarly converted into the 2-thiocytosine- and 4-N-methyl-2-thiocytosine-derived d4 nucleosides 11b and 23 in 51 and 50percent overall yield, respectively.Finally, the ethoxy-oxetane 12b was converted into the corresponding amino- and methylamino-oxetanes 25a and 25b in 74 and 83percent yield, respectively.The latter compound, 25b, was succesively converted into the 2-N-methylisocytosine-derived d4 nucleoside 26b in 62percent yield.

Nucleoside Sultones: Synthons for the Preparation of Novel Nucleotide Analogues. 1. Synthesis and Ring-Opening Reactions

Treatment of either the 5'-O-tosyl or the 5'-O-mesyl derivative of 3'-O-mesylthymidine with lithium acetylide-ethylenediamine complex in DMSO affords the intramolecular 6,3-ester of 1,2,5,6-tetradeoxy-1-(3,4-dihydro-5-methyl-2,4-dioxo-1(2H)-pyrimidinyl)-β-D-erythro-hexofuranuronosulfonic acid (2).Similarly, the 5'-O-tosyl or 5'-O-mesyl derivative of 1-(2-deoxy-3-O-mesyl-β-D-threo-pentofuranosyl)thymine affords the intramolecular 6,3-ester of 1,2,5,6-tetradeoxy-1-(3,4-dihydro-5-methyl-2,4-dioxo-1(2H)-pyrimidinyl)-β-D-threo-hexofuranuronosulfonic acid (5).Sultone 5 reacts with a variety of nucleophiles to afford good yields of the corresponding 3'-substituted sulfonate salts (6, 7, 9, and 10) and, in some cases, the unsaturated nucleoside 8.Sultone 2 was generally much less susceptible to ring opening by nucleophiles.However, in the presence of base, nucleophilic substitution with azide ion did proceed via the intermediate anhydronucleoside, 11, to afford 6.Reaction of 2 with EtOH-NaOH afforded a 1:1 mixture of the epimeric 3'-hydroxy compounds 9 and 12.The above sulfonate salts represent interesting new isosteres of nucleoside 5'-O-phosphates.