【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 |