84414-90-4

Usage

Uses

Used in Pharmaceutical Industry:
1-(2,3-DIDEOXY-A-D-GLYCERO-PENT-2-ENOFURANOSYL)THYMINE is used as an antiviral agent for the prevention and treatment of HIV/AIDS. It works by inhibiting the replication of the virus, thereby reducing the viral load in the body and slowing down the progression of the disease.
As a component of antiretroviral therapy:
1-(2,3-DIDEOXY-A-D-GLYCERO-PENT-2-ENOFURANOSYL)THYMINE is used in combination with other antiretroviral drugs to form highly active antiretroviral therapy (HAART) regimens. These combination therapies are more effective in controlling the virus and reducing the risk of drug resistance compared to monotherapy.
For research purposes:
1-(2,3-DIDEOXY-A-D-GLYCERO-PENT-2-ENOFURANOSYL)THYMINE is also used in research settings to study the mechanisms of action of nucleoside analogs and their potential applications in the development of new antiviral drugs.

Synthetic route

1-((2S,3R,5S)-3-Bromo-5-hydroxymethyl-tetrahydro-furan-2-yl)-5-methyl-1H-pyrimidine-2,4-dione (134660-13-2) → 1-(2,5-anhydro-3-deoxy-α-D-threo-pentofuranosyl)thymine (134660-21-2) + 1-(2,3-dideoxy-α-D-glycero-pent-2-enofuranosyl)thymine (84414-90-4)

Conditions	Yield
With methanol; sodium methylate for 30h; Heating;	A 50% B 20%

5-Methyl-1-((S)-5-trityloxymethyl-2,5-dihydro-furan-2-yl)-1H-pyrimidine-2,4-dione → 1-(2,3-dideoxy-α-D-glycero-pent-2-enofuranosyl)thymine (84414-90-4) + stavudin (3056-17-5)

Conditions	Yield
With Dowex R 50W; hydrogen cation In methanol Yield given. Yields of byproduct given;

D-2-deoxyribose (452-51-7, 13046-70-3, 29780-54-9, 36792-87-7, 36792-88-8, 113890-35-0, 113890-38-3) → 1-(2,3-dideoxy-α-D-glycero-pent-2-enofuranosyl)thymine (84414-90-4)

Conditions	Yield
Multi-step reaction with 6 steps 1: conc. HCl / dimethylformamide / Ambient temperature 2: 91 percent / imidazole / CH2Cl2 3: pyridine 4: DBU 5: 8 percent / NBS, 2,4-(trimethylsilyloxy)-6-methyl-pyrimidine, mol sieves 4A / CH2Cl2 / 0 °C 6: Dowex R 50W, H(1+) form / methanol View Scheme
Multi-step reaction with 6 steps 1: conc. HCl / dimethylformamide / Ambient temperature 2: 91 percent / imidazole / CH2Cl2 3: pyridine 4: DBU 5: 83 percent / NBS, mol. sieves 4A / CH2Cl2 / -78 °C 6: Dowex R 50W, H(1+) form / methanol View Scheme
Multi-step reaction with 6 steps 1: conc. HCl / Ambient temperature 2: 91 percent / imidazole / CH2Cl2 3: pyridine 4: DBU 5: 8 percent / NBS, 2,4-(trimethylsilyloxy)-6-methyl-pyrimidine, mol sieves 4A / CH2Cl2 / 0 °C 6: Dowex R 50W, H(1+) form / methanol View Scheme
Multi-step reaction with 6 steps 1: conc. HCl / Ambient temperature 2: 91 percent / imidazole / CH2Cl2 3: pyridine 4: DBU 5: 83 percent / NBS, mol. sieves 4A / CH2Cl2 / -78 °C 6: Dowex R 50W, H(1+) form / methanol View Scheme

phenyl 2-deoxy-1-thio-D-erythro-pentofuranoside (183075-04-9) → 1-(2,3-dideoxy-α-D-glycero-pent-2-enofuranosyl)thymine (84414-90-4)

Conditions	Yield
Multi-step reaction with 5 steps 1: 91 percent / imidazole / CH2Cl2 2: pyridine 3: DBU 4: 8 percent / NBS, 2,4-(trimethylsilyloxy)-6-methyl-pyrimidine, mol sieves 4A / CH2Cl2 / 0 °C 5: Dowex R 50W, H(1+) form / methanol View Scheme
Multi-step reaction with 5 steps 1: 91 percent / imidazole / CH2Cl2 2: pyridine 3: DBU 4: 83 percent / NBS, mol. sieves 4A / CH2Cl2 / -78 °C 5: Dowex R 50W, H(1+) form / methanol View Scheme

(2R,3S)-5-Phenylsulfanyl-2-trityloxymethyl-tetrahydro-furan-3-ol (182957-26-2) → 1-(2,3-dideoxy-α-D-glycero-pent-2-enofuranosyl)thymine (84414-90-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: pyridine 2: DBU 3: 8 percent / NBS, 2,4-(trimethylsilyloxy)-6-methyl-pyrimidine, mol sieves 4A / CH2Cl2 / 0 °C 4: Dowex R 50W, H(1+) form / methanol View Scheme
Multi-step reaction with 4 steps 1: pyridine 2: DBU 3: 83 percent / NBS, mol. sieves 4A / CH2Cl2 / -78 °C 4: Dowex R 50W, H(1+) form / methanol View Scheme

Trifluoro-methanesulfonic acid (2R,3S)-5-phenylsulfanyl-2-trityloxymethyl-tetrahydro-furan-3-yl ester → 1-(2,3-dideoxy-α-D-glycero-pent-2-enofuranosyl)thymine (84414-90-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: DBU 2: 8 percent / NBS, 2,4-(trimethylsilyloxy)-6-methyl-pyrimidine, mol sieves 4A / CH2Cl2 / 0 °C 3: Dowex R 50W, H(1+) form / methanol View Scheme
Multi-step reaction with 3 steps 1: DBU 2: 83 percent / NBS, mol. sieves 4A / CH2Cl2 / -78 °C 3: Dowex R 50W, H(1+) form / methanol View Scheme

(S)-2-Phenylsulfanyl-5-trityloxymethyl-2,5-dihydro-furan (190725-02-1) → 1-(2,3-dideoxy-α-D-glycero-pent-2-enofuranosyl)thymine (84414-90-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 8 percent / NBS, 2,4-(trimethylsilyloxy)-6-methyl-pyrimidine, mol sieves 4A / CH2Cl2 / 0 °C 2: Dowex R 50W, H(1+) form / methanol View Scheme
Multi-step reaction with 2 steps 1: 83 percent / NBS, mol. sieves 4A / CH2Cl2 / -78 °C 2: Dowex R 50W, H(1+) form / methanol View Scheme

(2R,5S)-2-Phenylsulfanyl-5-trityloxymethyl-2,5-dihydro-furan → 1-(2,3-dideoxy-α-D-glycero-pent-2-enofuranosyl)thymine (84414-90-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 72 percent / NBS, mol. sieves 4A / CH2Cl2 / -78 °C 2: Dowex R 50W, H(1+) form / methanol View Scheme

(2S,5S)-2-Phenylsulfanyl-5-trityloxymethyl-2,5-dihydro-furan → 1-(2,3-dideoxy-α-D-glycero-pent-2-enofuranosyl)thymine (84414-90-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 98 percent / NBS, mol. sieves 4A / CH2Cl2 / -78 °C 2: Dowex R 50W, H(1+) form / methanol View Scheme

2,4-bis(trimethylsiloxy)-5-methylpyrimidine (7288-28-0) → 1-(2,3-dideoxy-α-D-glycero-pent-2-enofuranosyl)thymine (84414-90-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 83 percent / NBS, mol. sieves 4A / CH2Cl2 / -78 °C 2: Dowex R 50W, H(1+) form / methanol View Scheme
Multi-step reaction with 2 steps 1: 72 percent / NBS, mol. sieves 4A / CH2Cl2 / -78 °C 2: Dowex R 50W, H(1+) form / methanol View Scheme
Multi-step reaction with 2 steps 1: 98 percent / NBS, mol. sieves 4A / CH2Cl2 / -78 °C 2: Dowex R 50W, H(1+) form / methanol View Scheme

methyl 2,3-dideoxy-5-O-(4-methylbenzoyl)-D-glycero-pentofuranoside (133635-44-6) → 1-(2,3-dideoxy-α-D-glycero-pent-2-enofuranosyl)thymine (84414-90-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: 60 percent / Br2, CaCO3 / diethyl ether / 1 h / Heating 2: 68 percent / trimethylsilyl triflate / acetonitrile / 24 h 3: 30 percent / NaOMe, MeOH / 3 h / Ambient temperature 4: 20 percent / NaOMe, MeOH / 30 h / Heating View Scheme

methyl 2-bromo-2,3-dideoxy-5-O-(4-methylbenzoyl)-D-erythropentofuranoside (134660-06-3) → 1-(2,3-dideoxy-α-D-glycero-pent-2-enofuranosyl)thymine (84414-90-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: 68 percent / trimethylsilyl triflate / acetonitrile / 24 h 2: 30 percent / NaOMe, MeOH / 3 h / Ambient temperature 3: 20 percent / NaOMe, MeOH / 30 h / Heating View Scheme

4-Methyl-benzoic acid (2S,4R)-4-bromo-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethyl ester (134660-10-9, 134660-42-7) → 1-(2,3-dideoxy-α-D-glycero-pent-2-enofuranosyl)thymine (84414-90-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 30 percent / NaOMe, MeOH / 3 h / Ambient temperature 2: 20 percent / NaOMe, MeOH / 30 h / Heating View Scheme

1-(2,3-dideoxy-α-D-glycero-pent-2-enofuranosyl)thymine (84414-90-4) → 1-(2,3-didehydro-2,3-dideoxy-β-d-pentofuranosyl-4-carboxy)thymine

Conditions	Yield
With ruthenium(III) chloride trihydrate; potassium persulfate; potassium hydroxide at 20℃; for 8h;	50%

Upstream product

• 143422-74-6 ((2R,3S)-5-Methoxy-3-phenylselanyl-tetrahydro-furan-2-yl)-methanol 
• 7288-28-0 2,4-bis(trimethylsiloxy)-5-methylpyrimidine 
• 134660-13-2 1-((2S,3R,5S)-3-Bromo-5-hydroxymethyl-tetrahydro-furan-2-yl)-5-methyl-1H-pyrimidine-2,4-dione 
• 452-51-7 D-2-deoxyribose 
• 77421-68-2 S'-acetyl-d4T 
• 134660-10-9 4-Methyl-benzoic acid (2S,4R)-4-bromo-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethyl ester 
• 134660-06-3 methyl 2-bromo-2,3-dideoxy-5-O-(4-methylbenzoyl)-D-erythropentofuranoside 
• 133635-44-6 methyl 2,3-dideoxy-5-O-(4-methylbenzoyl)-D-glycero-pentofuranoside 
• 190725-02-1 (S)-2-Phenylsulfanyl-5-trityloxymethyl-2,5-dihydro-furan 
• 182957-26-2 (2R,3S)-5-Phenylsulfanyl-2-trityloxymethyl-tetrahydro-furan-3-ol 
• 183075-04-9 phenyl 2-deoxy-1-thio-D-erythro-pentofuranoside 
• 139212-86-5 methyl 5-O-tert-butyldiphenylsilyl-2,3-dideoxy-3-iodo-D-threo-pentofuranoside 
• 3444-09-5 1,3-bis(trimethylsilyl)thymine 
• 143422-80-4 5'-acetyl-3'-selenophenylthymidine 

Downstream Products

• 71454-17-6 5'-O-tosyl-3'-deoxy-2'-thymidinene 

Relevant academic research and scientific papers

Facile synthesis of 2',3'-unsaturated nucleosides from 2-deoxyribose

A straightforward approach for the synthesis of 2',3'-unsaturated nucleosides starting from 2-deoxyribose is described. This novel route involves two new methods; (1) preparation of 2-deoxy-1-thioribofuranoside by direct condensation of 2-deoxyribose and thiophenol, (2) formation of the nucleoside skeleton by the direct coupling of 2,3-unsaturated 1-thiopentofuranoside with pyrimidine bases.

Synthesis of antiviral nucleosides from crotonaldehyde. Part 3. Total synthesis of didehydrodideoxythymidine (d4T)

The total synthesis of the antiviral agent d4T 3 from the epoxyalcohol 2, itself derived from crotonaldehyde 1, in 6 steps and 18% overall yield is described.

Synthesis of 2'-azido, 2,2'-anhydro and 2',5'-anhydro nucleosides with potential anti-HIV activity

Reaction of methyl 2-bromo-2,3-dideoxy-5-O-(4-methylbenzoyl)-D-erythro-pentofuranoside (7) with silylated uracils 9 using trimethylsilyl triflate as catalyst afforded the corresponding 2'-bromonucleosides 10. 2,3-Didehydro sugar 8 was prepared by heating 7 with sodium azide in dimethylformamide. 2,2'-Anhydronucleosides 1 were prepared by treating the nucleosides 10 with sodium methoxide at room temperature. 1-(2-Azido-2,3-dideoxy-β-D-threo-pentofuranosyl)thymine (15) and its α-anomer (16) were prepared by treating 10c with sodium azide and subsequently methanolic ammonia. Treatment of 1-(2-bromo-2,3-dideoxy-α-D-erythro-pentofuranosyl)thymine (11c) with excess of sodium methoxide under reflux gave the corresponding 2',5'-anhydro nucleoside 17.

New synthesis of 2',3'-didehydro-2',3'-dideoxynucleosides.

The 3'-iodonucleoside 4 and the 3'-O-methylsulfonylthymidine 9 have been synthesized by condensation of silylated uracils 2 with methyl 5-O-tert-butyldiphensilyl-2,3-dideoxy-3-iodo-D-threo-pentofuran oside (3) and methyl 5-O-tert-butyldiphenylsilyl-2-deoxy-3-methylsulfonyl-D-erythro- pentofuranoside (8), respectively. The nucleoside 4 and 9 produced the corresponding 2',3'-didehydro-2',3'-dideoxynucleosides 5 in an elimination reaction on treatment with sodium methoxide. The compounds 5b showed no antiviral activity against HIV-1.