(1S,2R)-4-methylene-2-([[(E)-3-phenyl-2-propenyl]oxy]carbonyl)cyclopentanecarboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】27283

【品名】(1S,2R)-4-methylene-2-([[(E)-3-phenyl-2-propenyl]oxy]carbonyl)cyclopentanecarboxylic acid

【CA登记号】

【分子式】C₁₇H₁₈O₄

【分子量】286.32752

【元素组成】C 71.31% H 6.34% O 22.35%

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：(XXI)

Cyclization of the tetracarboxylic acid (XV) gives 4-oxocyclopentane-1,2-dicarboxylic acid (XVI), which is esterified with ethanol and sulfuric acid to yield the diester (XVII). Reaction of diester (XVII) with methyl-(triphenyl)phosphonium bromide and t-BuOK in THF affords 4-methylenecyclopentane-1,2-dicarboxylic acid diethyl ester (XVIII), which is hydrolyzed with KOH in THF/water to provide the corresponding free acid (XIX). The anhydrization of (XIX) by means of propionic anhydride at 135 C gives anhydride (III), which is submitted to an enantioselective quinine-mediated alcoholysis with 3-phenyl-2-propen-1-ol (XX) to yield (1R,2S)-2-amino-4-methylenecyclopentane-1-carboxylic acid 3-phenyl-2-propenyl monoester (XXI). Degradation of the free carboxylic acid group of (XXI) by means of DPPA, TEA and alcohol (XX) in hot toluene affords carbamate (XXII), which is finally fully deprotected with Pd(OAc)2 and PPh3 in ethanol.

参考文献中间体

合成目标

【1】 Mittendorf, J.; Kunisch, F.; Matzke, M.; Militzer, H.-C.; Schmidt, A.; Schonfeld, W.; Novel antifungal beta-amino acids: Synthesis and activity against Candida albicans. Bioorg Med Chem Lett 2003, 13, 3, 433.
【2】 Sorbera, L.A.; Castañer, J.; Bozzo, J.; PLD-118. Drugs Fut 2002, 27, 11, 1049.
【3】 Schoenfeld, W.; Discovery, synthesis and SAR of beta-amino acid BAY 10-888/PLD-118, a novel antifungal for treatment of yeast infections. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-811.
【4】 Mittendorf, J. (Bayer AG); Efficient and highly enantioselective process for the preparation of enantiomerically pure cyclopentane-beta-amino acids . EP 0805145 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(III)	56629	(3aR,6aS)-5-methylenetetrahydro-1H-cyclopenta[c]furan-1,3(3aH)-dione		C₈H₈O₃	详情	详情
(XV)	56634	1,2,3,4-butanetetracarboxylic acid;1,2,3,4-Tetracarboxybutane	1703-58-8	C₈H₁₀O₈	详情	详情
(XVI)	56635	4-oxo-1,2-cyclopentanedicarboxylic acid		C₇H₈O₅	详情	详情
(XVII)	56636	diethyl 4-oxo-1,2-cyclopentanedicarboxylate		C₁₁H₁₆O₅	详情	详情
(XVIII)	56638	diethyl 4-methylene-1,2-cyclopentanedicarboxylate		C₁₂H₁₈O₄	详情	详情
(XIX)	56639	4-methylene-1,2-cyclopentanedicarboxylic acid		C₈H₁₀O₄	详情	详情
(XX)	13951	(E)-3-Phenyl-2-propen-1-ol	104-54-1	C₉H₁₀O	详情	详情
(XXI)	27283	(1S,2R)-4-methylene-2-([[(E)-3-phenyl-2-propenyl]oxy]carbonyl)cyclopentanecarboxylic acid		C₁₇H₁₈O₄	详情	详情
(XXII)	56637	(E)-3-phenyl-2-propenyl (1R,2S)-4-methylene-2-{[({[(E)-3-phenyl-2-propenyl]oxy}carbonyl)amino]carbonyl}cyclopentanecarboxylate		C₂₇H₂₇NO₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The previously reported chiral cyclopentanedicarboxylic acid monoester (I) was converted to the mixed anhydride (II) by treatment with ethyl chloroformate in the presence of triethylamine. Reduction of the mixed anhydride (II) with NaBH4 in cold MeOH produced the corresponding alcohol, which, under the reaction conditions, gave rise to the bicyclic lactone (III). Then, the lithium enolate generated from lactone (III) and lithium hexamethyldisilazide was alkylated with 2-(bromomethyl)naphthalene (IV) to produce the title compound.

参考文献中间体

合成目标

【1】 Horváth, E.; De Vry, J.-M.-V.; Baumgarten, J.; Schreiber, R.; Lensky, S.; Müller, T.; Stropp, U.; Voerste, A.; Müller, G.; Antonicek, H.-P.; Stolle, A.; Von dem Bruch, K. (Bayer AG); Substd. alpha,beta-anellated butyrolactones. DE 19801646; EP 1047684; WO 9936416 .

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)	27283	(1S,2R)-4-methylene-2-([[(E)-3-phenyl-2-propenyl]oxy]carbonyl)cyclopentanecarboxylic acid		C₁₇H₁₈O₄	详情	详情
(II)	51107			C₂₀H₂₂O₆	详情	详情
(III)	51108	(3aS,6aR)-5-methylenehexahydro-1H-cyclopenta[c]furan-1-one		C₈H₁₀O₂	详情	详情
(IV)	35612	2-(bromomethyl)naphthalene	939-26-4	C₁₁H₉Br	详情	详情

Extended Information