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【结 构 式】 
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【药物名称】OMPT, LXR-1035 【化学名称】9(Z)-Octadecenoic acid 2-methoxy-3-(thiophosphonooxy)propyl ester 【CA登记号】213738-69-3 【 分 子 式 】C22H43O6PS 【 分 子 量 】466.62221 |
【开发单位】LXR Biotechnology (Originator) 【药理作用】Acute Myocardial Infarction, Treatment of, CARDIOVASCULAR DRUGS, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, Apoptosis Inhibitors, Cell Adhesion Inhibitors, Lysophospholipid edg7 (LPA3) Receptor Agonists |
合成路线1
Silylation of 1-O-benzylglycerol (I) with tert-butyldimethylsilyl chloride afforded the 1,3-diprotected glycerol (II). After methylation of the free secondary hydroxyl of (II) using MeI and NaH to yield (III), its O-benzyl protecting group was cleaved by hydrogenolysis, yielding (IV). Acylation of alcohol (IV) with oleoyl chloride (V) in the presence of pyridine provided the corresponding ester (VI). Desilylation of (VI) to give alcohol (VII) was carried out by treatment with tetrabutylammonium fluoride. Alcohol (VII) was then condensed with (2-cyanoethyl)-N,N,N',N'-tetraisopropylphosphorodiamidite (VIII) in the presence of 3-hydroxypropionitrile and tetrazole, followed by reaction with elemental sulfur to furnish the thiophosphate (IX). Finally, cleavage of the cyanoethyl ester groups with Et3N and bis(trimethylsilyl)acetamide provided the title compound.
| 【1】 Boyd, E.A.; Umansky, S.R.; Baxter, A.D.; Price, S.; Goddard, J.G.; Picker, D.H.; Wijkmans, J.C.H.M. (Evotec Biosystems AG; LXR Biotechnology Inc.); Compsns. containing lysophosphatidic acids which inhibit apoptosis and uses thereof. WO 9947101 . |
| 【2】 Vmansky, S.R.; Goddard, J.G.; Picker, D.H.; Bathurst, I.C.; Bradley, J.D.; Foehr, M.W. (LXR Biotechnology Inc.); Compsns. containing lysophosphatidic acids which inhibit apoptosis and uses thereof. WO 9841213 . |
| 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) | 12699 | (2S)-3-(Benzyloxy)-1,2-propanediol; (S)-(-)-1-Benzylglycerol | 17325-85-8 | C10H14O3 | 详情 | 详情 |
| (II) | 48651 | 1-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-propanol | C16H28O3Si | 详情 | 详情 | |
| (III) | 48652 | benzyl 3-[[tert-butyl(dimethyl)silyl]oxy]-2-methoxypropyl ether; [3-(benzyloxy)-2-methoxypropoxy](tert-butyl)dimethylsilane | C17H30O3Si | 详情 | 详情 | |
| (IV) | 48653 | 3-[[tert-butyl(dimethyl)silyl]oxy]-2-methoxy-1-propanol | C10H24O3Si | 详情 | 详情 | |
| (V) | 28280 | Oleoyl chloride; (E)-9-Octadecenoyl chloride | C18H33ClO | 详情 | 详情 | |
| (VI) | 48654 | 3-[[tert-butyl(dimethyl)silyl]oxy]-2-methoxypropyl (Z)-9-octadecenoate | C28H56O4Si | 详情 | 详情 | |
| (VII) | 48655 | 3-hydroxy-2-methoxypropyl (Z)-9-octadecenoate | C22H42O4 | 详情 | 详情 | |
| (VIII) | 48656 | 2-Cyanoethyl N,N,N',N'-tetraisopropylphosphoramidite; 2-Cyanoethyl N,N,N',N'-tetraisopropylphosphorodiamidite; Bis(diisopropylamino)-2-cyanoethoxyphosphine | 102691-36-1 | C15H32N3OP | 详情 | 详情 |
| (IX) | 48657 | 3-([(2-cyanoethoxy)[(2-cyanoethyl)sulfanyl]phosphoryl]oxy)-2-methoxypropyl (Z)-9-octadecenoate | C28H49N2O6PS | 详情 | 详情 |