【结 构 式】 |
【分子编号】29763 【品名】5-[(3aR,5R,6R,6aR)-3a-methyl-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]-6-[(E,3S)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-octenyl]hexahydro-2(1H)-pentalenylidene]pentanoic acid 【CA登记号】 |
【 分 子 式 】C34H56O6 【 分 子 量 】560.81504 【元素组成】C 72.82% H 10.06% O 17.12% |
合成路线1
该中间体在本合成路线中的序号:(VI)Treatment of the optically pure lactone (I) with lithium dimethyl methylphosphonate in tetrahydrofuran gives hemiacetal (II), which is oxidized to the diketone (III) using Jones' reagent in acetone. Then in the key step, compound (III) cyclizes to enone (IV) using potassium carbonate and 18-crown-6 in warm toluene. Lithium dimethyl cuprate addition to enone (IV) in ether gives ketone (V), which is converted to acid (VI) (a 1:1 mixture of E and Z olefins at C-5) using (4-carboxybutyl)triphenylphosphorane in dimethyl sulfoxide. Cleavage of the alcohol-protecting groups in (VI) with an acetic acid-water-tetrahydrofuran mixture followed by chromatography to remove the 5-E isomer affords 9-methylcarbacyclin (VII). Finally, treatment of (VII) with calcium oxide in tetrahydrofuran gives U-61431F (ciprostene calcium).
【1】 Aristoff, P.A.; Harrison, A.W.; Johnson, P.D.; Synthesis of 9-subtituted cabacyclin analogues. J Org Chem 1983, 48, 5341. |
【2】 Aristoff, P.A.; Practical synthesis of 6a-carbaprostaglandin I2. J Org Chem 1981, 46, 1954. |
【3】 Aristoff, P.A. (Pharmacia Corp.); Composition and process. US 4420632 . |
【4】 Aistoff, P.A.; Ciprostene Calcium. Drugs Fut 1985, 10, 11, 900. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(A) | 29720 | [(dimethoxyphosphoryl)methyl]lithium | C3H8LiO3P | 详情 | 详情 | |
(B) | 29762 | sodium 5-(triphenylphosphoranylidene)pentanoate | C23H22NaO2P | 详情 | 详情 | |
(I) | 29757 | (3aR,4S,5R,6aS)-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]-4-[(E,3S)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-octenyl]hexahydro-2H-cyclopenta[b]furan-2-one | C27H44O6 | 详情 | 详情 | |
(II) | 29758 | dimethyl ((3aR,4S,5R,6aS)-2-hydroxy-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]-4-[(E,3S)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-octenyl]hexahydro-2H-cyclopenta[b]furan-2-yl)methylphosphonate | C30H53O9P | 详情 | 详情 | |
(III) | 29759 | dimethyl 2-oxo-3-((4R,5R)-2-oxo-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]-4-[(E,3S)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-octenyl]tetrahydro-3-furanyl)propylphosphonate | C29H49O10P | 详情 | 详情 | |
(IV) | 29760 | (3aR,4R,5R)-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]-4-[(E,3S)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-octenyl]-3a,4,5,6-tetrahydro-2(3H)-pentalenone | C28H44O5 | 详情 | 详情 | |
(V) | 29761 | (3aR,5R,6R,6aR)-3a-methyl-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]-6-[(E,3S)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-octenyl]hexahydro-2(1H)-pentalenone | C29H48O5 | 详情 | 详情 | |
(VI) | 29763 | 5-[(3aR,5R,6R,6aR)-3a-methyl-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]-6-[(E,3S)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-octenyl]hexahydro-2(1H)-pentalenylidene]pentanoic acid | C34H56O6 | 详情 | 详情 | |
(VII) | 29764 | 5-[(3aS,5R,6R,6aR)-5-hydroxy-6-[(E,3S)-3-hydroxy-1-octenyl]-3a-methylhexahydro-2(1H)-pentalenylidene]pentanoic acid | C22H36O4 | 详情 | 详情 |