bis(tBuSATE)AZT-MP, UA-428, -Drug Synthesis Database

【结构式】

【药物名称】bis(tBuSATE)AZT-MP, UA-428

【化学名称】3'-Azido-5'-O-[bis[2-(S-pivaloylsulfanyl)ethoxy]phosphoryl]-3'-deoxythymidine

【CA登记号】168777-50-2

【分子式】C₂₄H₃₈N₅O₉PS₂

【分子量】635.70036

【开发单位】Katholieke Universiteit Leuven (Originator), Université Montpellier II (Originator)

【药理作用】AIDS Medicines, Anti-HIV Agents, ANTIINFECTIVE THERAPY, Chemical Delivery Systems, DRUG DELIVERY, Drug Delivery Systems, Reverse Transcriptase Inhibitors

合成路线1 合成路线2

合成路线1

The esterification of 2,2-dimethyl-thiopropionic acid (I) with 2-iodoethanol (II) and DBU in toluene gives the corresponding thioester (III), which is condensed with diisopropylamidophosphoryl dichloride (IV) by means of TEA in THF to afford the phosphoramidite (V). Finally, this compound is condensed with AZT (VI) by means of 1H-tetrazole and MCPBA or 1H-tetrazole and tert-butyl peroxide, both cases in THF.

参考文献中间体

【1】 Lefebvre, I.; et al.; Mononucleoside phosphotriester derivatives with S-acyl-2-thioethyl bioreversible phosphate-protecting groups: Intracellular delivery of 3'-azido-2',3'-dideoxythymidine 5'-monophosphate. J Med Chem 1995, 38, 20, 3941.
【2】 Lannuzel, M.; et al.; Synthesis of the tBuSATE pronucleotide of AZT by two different synthetic approaches. Nucleosides Nucleotides 1999, 18, 4-5, 1001.
【3】 Lefebvre, I.; et al.; Synthesis, descomposition pathways and "in vitro" evaluation of bioreversible phosphotriesters of AZT. Nucleosides Nucleotides 1995, 14, 3-5, 763.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	38257	2,2-dimethylpropanethioic S-acid		C₅H₁₀OS	详情	详情
(II)	38258	2-iodo-1-ethanol	624-76-0	C₂H₅IO	详情	详情
(III)	38259	S-(2-hydroxyethyl) 2,2-dimethylpropanethioate		C₇H₁₄O₂S	详情	详情
(IV)	38260			C₆H₁₄Cl₂NOP	详情	详情
(V)	38261	S-[4-(diisopropylamino)-10,10-dimethyl-4,9-dioxo-3,5-dioxa-8-thia-4lambda(5)-phosphaundec-1-yl] 2,2-dimethylpropanethioate		C₂₀H₄₀NO₅PS₂	详情	详情
(VI)	25317	1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione	101703-35-9	C₁₀H₁₃N₅O₄	详情	详情

合成路线2

The phosphorylation of AZT (VI) with POCl3 trimethyl phosphate gives the 5'-O-phosphate (VII), which is then condensed with the previously described thioester (III) by means of Tps-Cl in pyridine.

参考文献中间体

【1】 Lannuzel, M.; et al.; Synthesis of the tBuSATE pronucleotide of AZT by two different synthetic approaches. Nucleosides Nucleotides 1999, 18, 4-5, 1001.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(III)	38259	S-(2-hydroxyethyl) 2,2-dimethylpropanethioate		C₇H₁₄O₂S	详情	详情
(VI)	25317	1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione	101703-35-9	C₁₀H₁₃N₅O₄	详情	详情
(VII)	38262	[(2S,3S,5R)-3-azido-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl]methyl dihydrogen phosphate		C₁₀H₁₄N₅O₇P	详情	详情

Extended Information