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【结 构 式】 
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【分子编号】33046 【品名】S-[(2R,3R)-2-(azidomethyl)tetrahydro-3-furanyl] ethanethioate 【CA登记号】 |
【 分 子 式 】C7H11N3O2S 【 分 子 量 】201.24936 【元素组成】C 41.78% H 5.51% N 20.88% O 15.9% S 15.93% |
合成路线1
该中间体在本合成路线中的序号：(XII)1,2-Dideoxy-D-ribose (IX) was converted to bismesylate (X) upon treatment with methanesulfonyl chloride and pyridine. Displacement of the primary mesylate group of (X) with LiN3 in DMF gave azide (XI). The secondary mesylate group was further displaced with potassium thioacetate to provide (XII). Thiol (XIII) was then prepared by hydrolysis of the thioester function with NaOMe in THF.
| 【1】 Lin, Y.-I.; Bitha, P.; Sakya, S.; Strohmeyer, T.W.; Bush, K. (American Cyanamid Co.); Novel 2-thiosubstd. carbapenems. CA 2118961; EP 0617036; JP 1994321948; US 5602118 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 33043 | (2R,3S)-2-(hydroxymethyl)tetrahydro-3-furanol | C5H10O3 | 详情 | 详情 | |
| (X) | 33044 | (2R,3S)-2-[[(methylsulfonyl)oxy]methyl]tetrahydro-3-furanyl methanesulfonate | C7H14O7S2 | 详情 | 详情 | |
| (XI) | 33045 | (2R,3S)-2-(azidomethyl)tetrahydro-3-furanyl methanesulfonate | C6H11N3O4S | 详情 | 详情 | |
| (XII) | 33046 | S-[(2R,3R)-2-(azidomethyl)tetrahydro-3-furanyl] ethanethioate | C7H11N3O2S | 详情 | 详情 | |
| (XIII) | 33047 | (2R,3R)-2-(azidomethyl)tetrahydro-3-furanthiol; (2R,3R)-2-(azidomethyl)tetrahydro-3-furanylhydrosulfide | C5H9N3OS | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XII)In an alternative procedure, deoxyribose (XIV) was reduced to 2-deoxy-D-erythropentitol (XV) with NaBH4. Acid-catalyzed cyclization of (XV) produced (IX), which was converted to triflate (XVI) using trifluoromethanesulfonic anhydride and pyridine. Displacement with tetrabutylammonium azide provided azido derivative (XVII). Further treatment with trifluoromethanesulfonic anhydride gave triflate (XVIII), which was then displaced with potassium thioacetate to yield thioester (XII). This was hydrolyzed with NaOMe as above to furnish thiol (XIII).
| 【1】 Lin, Y.-I.; Bitha, P.; Sakya, S.; Strohmeyer, T.W.; Bush, K. (American Cyanamid Co.); Novel 2-thiosubstd. carbapenems. CA 2118961; EP 0617036; JP 1994321948; US 5602118 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 33043 | (2R,3S)-2-(hydroxymethyl)tetrahydro-3-furanol | C5H10O3 | 详情 | 详情 | |
| (XII) | 33046 | S-[(2R,3R)-2-(azidomethyl)tetrahydro-3-furanyl] ethanethioate | C7H11N3O2S | 详情 | 详情 | |
| (XIII) | 33047 | (2R,3R)-2-(azidomethyl)tetrahydro-3-furanthiol; (2R,3R)-2-(azidomethyl)tetrahydro-3-furanylhydrosulfide | C5H9N3OS | 详情 | 详情 | |
| (XIV) | 33048 | (3S,4R)-3,4,5-trihydroxypentanal | 18546-37-7 | C5H10O4 | 详情 | 详情 |
| (XV) | 33049 | (2R,3S)-1,2,3,5-pentanetetrol | C5H12O4 | 详情 | 详情 | |
| (XVI) | 33050 | [(2R,3S)-3-hydroxytetrahydro-2-furanyl]methyl trifluoromethanesulfonate | C6H9F3O5S | 详情 | 详情 | |
| (XVII) | 33051 | (2R,3S)-2-(azidomethyl)tetrahydro-3-furanol | C5H9N3O2 | 详情 | 详情 | |
| (XVIII) | 33052 | (2R,3S)-2-(azidomethyl)tetrahydro-3-furanyl trifluoromethanesulfonate | C6H8F3N3O4S | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XII)A convergent synthesis was further developed. Azide (XII) was reduced to the corresponding amine (XXVIII) employing triethyl phosphite. Hydrolysis of the thioacetate ester of (XXVIII) then gave thiol (XXIX). Coupling of (XXIX) with protected valine succinimidyl ester (XXVI) produced amide (XXX). Condensation of (XXX) with carbapenem phosphate (VIII) yielded adduct (XXXI). The p-nitrobenzyl esters were finally deprotected by catalytic hydrogenation.
| 【1】 Lin, Y.I.; Li, Z.; Bitha, P.; Convergent synthesis of oral 1beta-methylcarbapenems. J Antibiot 1999, 52, 7, 643. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIII) | 13224 | 4-nitrobenzyl (4R,5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | 90776-59-3 | C29H27N2O10P | 详情 | 详情 |
| (XII) | 33046 | S-[(2R,3R)-2-(azidomethyl)tetrahydro-3-furanyl] ethanethioate | C7H11N3O2S | 详情 | 详情 | |
| (XXVI) | 33058 | 4-nitrobenzyl (1S)-1-[[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl]-2-methylpropylcarbamate | C17H19N3O8 | 详情 | 详情 | |
| (XXVIII) | 33060 | S-[(2R,3R)-2-(aminomethyl)tetrahydro-3-furanyl] ethanethioate | C7H13NO2S | 详情 | 详情 | |
| (XXIX) | 33061 | (2R,3R)-2-(aminomethyl)tetrahydro-3-furanylhydrosulfide; (2R,3R)-2-(aminomethyl)tetrahydro-3-furanthiol | C5H11NOS | 详情 | 详情 | |
| (XXX) | 33062 | 4-nitrobenzyl (1S)-2-methyl-1-[([[(2R,3R)-3-sulfanyltetrahydro-2-furanyl]methyl]amino)carbonyl]propylcarbamate | C18H25N3O6S | 详情 | 详情 | |
| (XXXI) | 33063 | 4-nitrobenzyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-[[(2R,3R)-2-([[(2S)-3-methyl-2-([[(4-nitrobenzyl)oxy]carbonyl]amino)butanoyl]amino]methyl)tetrahydro-3-furanyl]sulfanyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | C35H41N5O12S | 详情 | 详情 |