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【结 构 式】

【药物名称】VPC-12249

【化学名称】3-[4-(Benzyloxy)phenyl]-2(S)-[9(Z)-octadecenamido]propyl dihydrogen phosphate

【CA登记号】

【 分 子 式 】C34H52NO6P

【 分 子 量 】601.77044

【开发单位】University of Virginia (Originator)

【药理作用】PHARMACOLOGICAL TOOLS, Lysophospholipid edg2 (LPA1) Receptor Antagonists, Lysophospholipid edg7 (LPA3) Receptor Antagonists

合成路线1

N-Boc-O-benzyltyrosine (I) was converted to the aminoalcohol derivative (III) via conversion to the mixed anhydride (II) with isobutyl chloroformate and subsequent reduction with NaBH4. Acid cleavage of the N-Boc protecting group of (III) gave the free amine (IV), which was acylated with oleoyl chloride (V) to afford amide (VI). Phosphitylation of (VI) with N,N-diisopropyl di-tert-butyl phosphoroamidite in the presence of tetrazole, followed by oxidation of the intermediate phosphite with hydrogen peroxide, furnished the phosphate (VII). The tert-butyl phosphate ester groups of (VII) were finally cleaved by treatment with trifluoroacetic acid.

1 Santos, W.L.; et al.; Structure-activity relationships of lysophosphatidic acid: Synthesis and analysis of EDG receptor agonists and antagonists. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 272.
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) 30396 (2S)-3-[4-(benzyloxy)phenyl]-2-[(tert-butoxycarbonyl)amino]propionic acid 54784-43-9 C21H25NO5 详情 详情
(II) 51294   C26H33NO7 详情 详情
(III) 21589 ethyl 3-cyano-3-[3-(cyclopentyloxy)-4-methoxyphenyl]propanoate C18H23NO4 详情 详情
(IV) 51290 (2S)-2-amino-3-[4-(benzyloxy)phenyl]-1-propanol C16H19NO2 详情 详情
(V) 51291 (Z)-9-hexadecenoyl chloride C16H29ClO 详情 详情
(VI) 51292 (Z)-N-[(1S)-1-[4-(benzyloxy)benzyl]-2-hydroxyethyl]-9-hexadecenamide C32H47NO3 详情 详情
(VII) 51293 (2S)-3-[4-(benzyloxy)phenyl]-2-[(Z)-9-hexadecenoylamino]propyl di(tert-butyl) phosphate C40H64NO6P 详情 详情
Extended Information