5-(triphenylphosphoranylidene)pentanoic acid -Drug Synthesis Database

【结构式】

【分子编号】37505

【品名】5-(triphenylphosphoranylidene)pentanoic acid

【CA登记号】

【分子式】C₂₃H₂₃O₂P

【分子量】362.408182

【元素组成】C 76.23% H 6.4% O 8.83% P 8.55%

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：(XIII)

The ketalization of cis-bicyclo[3.3.0]octane-3,7-dione (I) with ethylene glycol (A) and p-toluenesulfonic acid gives the diethyleneketal (II), which by controlled hydrolysis with acetic acid-THF-water is converted into the monoketal (III). Carboxylation of (III) with diethyl carbonate by means of NaH yields the ketoester (IV), which is reduced with sodium borohydride in ethanol to afford the hydroxyester (V). Protection of (V) with dimethyl-tert-butylsilyl chloride gives the silylether (VI), which is reduced with diisobutylaluminum hydride to the alcohol (VII). Oxidation of (VII) with pyridinium chlorochromate affords the aIdehyde (VIII), which by a Wittig reaction with the sodium salt of dimethyl 2-oxoheptylphosphonate (IX) is converted into the enone (X). The reduction of (X) with zinc borohydride yields the protected alcohol (XI), which is deprotected to the corresponding dihydroxyketone (XII) by treatment with acetic acid-THF-water. Finally, this compound is submitted to a Wittig reaction with the sodium salt of 4-carboxybutyltriphenylphosphorane (XIII) in DMS.

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】 Magolda, R.L.; Barnette, W.E.; Nicolaou, K.C.; Seitz, S.; Sipio, W.J.; Total synthesis of carboprostacyclin, a stable and biologically active analog of prostacyclin (PGI2). J Chem Soc Chem Commun 1978, 23, 1067-68.
【3】 Castaner, J.; Hillier, K.; Carbacyclin. Drugs Fut 1981, 6, 12, 753.

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)	11295	Polyethylene glycol;1,2-Ethanediol;Monoethylene glycol; Ethylene glycol	107-21-1	C₂H₆O₂	详情	详情
(I)	37496	tetrahydro-2,5(1H,3H)-pentalenedione		C₈H₁₀O₂	详情	详情
(II)	37497			C₁₂H₁₈O₄	详情	详情
(III)	11311	Perhydropentalene-2,5-dione mono ethyleneketal		C₁₀H₁₄O₃	详情	详情
(IV)	37498			C₁₃H₁₈O₅	详情	详情
(V)	37499			C₁₃H₂₀O₅	详情	详情
(VI)	37500			C₁₉H₃₄O₅Si	详情	详情
(VII)	37501			C₁₇H₃₂O₄Si	详情	详情
(VIII)	11315	(3'aS,4'R,5'R,6'aR)-5'-(tert-Butyldimethylsilyloxy)perhydrospiro[1,3-dioxolane-2,2'-pentalen]-4'-ylcarbaldehyde		C₁₇H₃₀O₄Si	详情	详情
(IX)	13738	dimethyl 2-oxoheptylphosphonate; Dimethyl (2-oxoheptyl)phosphonate	36969-89-8	C₉H₁₉O₄P	详情	详情
(X)	37502			C₂₄H₄₂O₄Si	详情	详情
(XI)	37503			C₂₄H₄₄O₄Si	详情	详情
(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

合成路线2

该中间体在本合成路线中的序号：(XIII)

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

Extended Information