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【结 构 式】

【药物名称】2-MPPA, GPI-5693, NAAL-1

【化学名称】2-(3-Sulfanylpropyl)pentanedioic acid

【CA登记号】254737-29-6

【 分 子 式 】C8H14O4S

【 分 子 量 】206.26238

【开发单位】Guilford Pharmaceuticals (Originator)

【药理作用】Diabetic Neuropathy, Agents for, ENDOCRINE DRUGS, Treatment of Diabetic Complications, NAALADase Inhibitors

合成路线1

Acylation of Meldrum's acid (I) with 3-tryphenylmethylsulfanyl)propionic acid (II) by means of DCC produces the intermediate adduct (III), which is subsequently reduced to the tritylsulfanyl derivative (IV) by using NaBH4/AcOH. Alkylation of (IV) with methyl 3-bromopropionate (V) in the presence of NaOMe provides the 5,5-disubstituted dioxanedione (VI). Basic hydrolysis of (VI) gives rise to the tricarboxylic acid (VII), which is further decarboxylated to (VIII) in hot DMSO. Finally the S-trityl protecting gropu is removed by treatment with trifluoroacetic acid and triisopropylsilane.

1 Jackson, P.F.; Slusher, B.S.; Majer, P.; Maclin, K.M.; Wang, E.; Lapidus, R.S. (Guilford Pharmaceuticals Inc.); NAALADase inhibitors useful as pharmaceutical cpds. and compsns.. JP 2002519408; US 6395718; WO 0001668 .
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) 14738 Meldrum's acid; 2,2-dimethyl-1,3-dioxane-4,6-dione;Malonic acid cyclic isopropylidene ester 2033-24-1 C6H8O4 详情 详情
(II) 63154 3-[(triphenylmethyl)sulfanyl]propanoic acid C22H20O2S 详情 详情
(III) 63155 5-{1-hydroxy-3-[(triphenylmethyl)sulfanyl]propylidene}-2,2-dimethyl-1,3-dioxane-4,6-dione C28H26O5S 详情 详情
(IV) 63156 2,2-dimethyl-5-{3-[(triphenylmethyl)sulfanyl]propyl}-1,3-dioxane-4,6-dione C28H28O4S 详情 详情
(V) 50285 3-Bromopropionic acid methyl ester; Methyl 3-bromopropionate 3395-91-3 C4H7BrO2 详情 详情
(VI) 63157 methyl 3-(2,2-dimethyl-4,6-dioxo-5-{3-[(triphenylmethyl)sulfanyl]propyl}-1,3-dioxan-5-yl)propanoate C32H34O6S 详情 详情
(VII) 63158 6-[(triphenylmethyl)sulfanyl]-1,3,3-hexanetricarboxylic acid C28H28O6S 详情 详情
(VIII) 63159 2-{3-[(triphenylmethyl)sulfanyl]propyl}pentanedioic acid C27H28O4S 详情 详情
Extended Information