(3aS,4S,5R,6aR)-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]-4-[(E,3S)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-octenyl]hexahydro-2(1H)-pentalenone -Drug Synthesis Database

【结构式】

【分子编号】37531

【品名】(3aS,4S,5R,6aR)-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]-4-[(E,3S)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-octenyl]hexahydro-2(1H)-pentalenone

【CA登记号】

【分子式】C₂₈H₄₆O₅

【分子量】462.67024

【元素组成】C 72.69% H 10.02% O 17.29%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(XXXV)

Reduction of (XXXIV) with LiAlH4, followed by oxidation with Collins reagent affords the bis(tetrahydropyranyl)ketone (XXXV) (which can also be obtained by reaction of dihydroxyketone (XII) with dihydropyran). The Wittig reaction of (XXXV) with phosphorane (XIII) gives the protected carbacyclin (XXXVI), which is finally deprotected in the usual way.

参考文献中间体

合成目标

【1】 Shibasaki, M.; Ikegami, S.; Ueda, J.; New synthetic routes to 9(O)-methanopostacyclin. A highly stable and biologically potent analog of prostacyclin. Tetrahedron Lett 1979, 5, 433-436.
【2】 Sugie, A.; Katsube, J.; Shimomura, H.; Yamamoto, H.; Synthetic studies on cyclopentane derivatives. Part 10. Stereocontrolled approaches to 9(O)-methanoprostacyclin. Tetrahedron Lett 1979, 28, 2607-10.
【3】 Castaner, J.; Hillier, K.; Carbacyclin. Drugs Fut 1981, 6, 12, 753.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XII)	37504	(3aS,4S,5R,6aR)-5-hydroxy-4-[(E,3S)-3-hydroxy-1-octenyl]hexahydro-2(1H)-pentalenone	C₁₆H₂₆O₃	详情	详情
(XIII)	37505	5-(triphenylphosphoranylidene)pentanoic acid	C₂₃H₂₃O₂P	详情	详情
(XXXIV)	37530	(1aS,1bS,2S,3R,4aR)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-2-[(E,3S)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-octenyl]octahydropentaleno[1,2-b]oxirene; (2S,3E)-4-[(1aS,1bS,2S,3R,4aR)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]octahydropentaleno[1,2-b]oxiren-2-yl]-2-pentyl-3-butenyl tetrahydro-2H-pyran-2-yl ether	C₂₈H₄₆O₅	详情	详情
(XXXV)	37531	(3aS,4S,5R,6aR)-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]-4-[(E,3S)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-octenyl]hexahydro-2(1H)-pentalenone	C₂₈H₄₆O₅	详情	详情
(XXXVI)	37532	5-[(3aS,4S,5R,6aR)-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]-4-[(E,3S)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-octenyl]hexahydro-2(1H)-pentalenylidene]pentanoic acid	C₃₃H₅₄O₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXXV)

Compound (L) is hydrolyzed with KOH and methylated with diazomethane to yield the diester (LI). The Dieckmann cyclization of (LI) by means of potassium tert-butoxide in THF yields the bicyclic ketoester (LII), which is decarboxylated by treatment with LiI in pyridine yielding the previously obtained bis tetrahydropyranylketone (XXXV). This compound can be deprotected to the dihydroxyketone (XII) with aqueous acetic acid.

参考文献中间体

合成目标

【1】 Sugie, A.; Katsube, J.; Shimomura, H.; Yamamoto, H.; Synthetic studies on cyclopentane derivatives. Part 10. Stereocontrolled approaches to 9(O)-methanoprostacyclin. Tetrahedron Lett 1979, 28, 2607-10.
【2】 Castaner, J.; Hillier, K.; Carbacyclin. Drugs Fut 1981, 6, 12, 753.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XII)	37504	(3aS,4S,5R,6aR)-5-hydroxy-4-[(E,3S)-3-hydroxy-1-octenyl]hexahydro-2(1H)-pentalenone	C₁₆H₂₆O₃	详情	详情
(XXXV)	37531	(3aS,4S,5R,6aR)-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]-4-[(E,3S)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-octenyl]hexahydro-2(1H)-pentalenone	C₂₈H₄₆O₅	详情	详情
(L)	37545	methyl 2-((1R,2S,3S,4R)-2-(2-nitriloethyl)-4-[(tetrahydro-2H-pyran-2-yloxy)methyl]-3-[(E,3S)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-octenyl]cyclopentyl)acetate	C₃₀H₄₉NO₆	详情	详情
(LI)	37546	methyl 2-((1R,2S,3S,4R)-2-(2-methoxy-2-oxoethyl)-4-[(tetrahydro-2H-pyran-2-yloxy)methyl]-3-[(E,3S)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-octenyl]cyclopentyl)acetate	C₃₁H₅₂O₈	详情	详情
(LII)	37547	methyl (1R,3aR,4R,5R,6aS)-2-oxo-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]-4-[(E,3S)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-octenyl]octahydro-1-pentalenecarboxylate	C₃₀H₄₈O₇	详情	详情

Extended Information