(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropionic acid -Drug Synthesis Database

【结构式】

【分子编号】31988

【品名】(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropionic acid

【CA登记号】

【分子式】C₁₆H₁₅NO₄

【分子量】285.29944

【元素组成】C 67.36% H 5.3% N 4.91% O 22.43%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：

A new synthesis of the side chain of paclitaxel has been described: The reaction of 2,3-epoxy-3-phenylpropionic acid methyl ester (I) with sodium azide in hot methanol/DMF/water gives 3-azido-2-hydroxy-3-phenylpropionic acid methyl ester (II), which is oxidized with Jones' reagent yielding 3-azido-2-oxo-3-phenylpropionic acid methyl ester (III). The reduction of (III) with Baker's yeast in water affords 3(RS)-azido-2(R)-hydroxy-3-phenylpropionic acid methyl ester (IV) as a diastereomeric mixture, which is resolved by spinning-plate chromatography in silicagel using ethyl acetate/pentane as solvent. The resulting (2R, 3S)-isomer (IV) is converted into the target compound by known methods (Adam, W. et al Tetrahedron Asymmetry, 1995, 6: 1047).

参考文献中间体

合成目标

【1】 Kayser, M.M.; et al.; Baker's yeast-mediated reductions of alpha-keto esters and an alpha-keto-beta-lactam. Two routes to the paclitaxel side chain. J Org Chem 1999, 64, 18, 6603.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
	31988	(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropionic acid	C₁₆H₁₅NO₄	详情	详情
(I)	32007	methyl 3-phenyl-2-oxiranecarboxylate	C₁₀H₁₀O₃	详情	详情
(II)	31984	methyl 3-azido-2-hydroxy-3-phenylpropanoate	C₁₀H₁₁N₃O₃	详情	详情
(III)	31985	methyl 3-azido-2-oxo-3-phenylpropanoate	C₁₀H₉N₃O₃	详情	详情
(IV)	31986	methyl (2R)-3-azido-2-hydroxy-3-phenylpropanoate	C₁₀H₁₁N₃O₃	详情	详情
(V)	31987	methyl (2R,3S)-3-azido-2-hydroxy-3-phenylpropanoate	C₁₀H₁₁N₃O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

The asymmetric dihydroxylation of trans-cinnamic acid ethyl ester (I) with AD mix alpha gives (2R,3S)-2,3-dihydroxy-3-phenylpropionic acid ethyl ester (II), which is submitted to the cyclic iminocarbonate rearrangement protocol with Bu4SnO, PhCO-NCS and MgI2 to yield the chiral oxazolidinone (III). The hydrolysis of (III) in refluxing 10% HCl affords (2R,3S)-3-amino-2-hydroxy-3-phenylpropionic acid (IV), which is finally N-benzoylated by means of benzoyl chloride and NaOH to provide the target side chain acid (V).

参考文献中间体

合成目标

【1】 Cho, G.Y.; et al.; Improving the regioselectivity in the cyclic iminocarbonate rearrangement: Enantioselective synthesis of the paclitaxel side chain. Bull Korean Chem Soc 2001, 22, 4, 432.

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)	54905	Cinnamic acid ethylester; Ethyl cinnamate		C₁₁H₁₂O₂	详情	详情
(II)	54906	ethyl (2R,3S)-2,3-dihydroxy-3-phenylpropanoate		C₁₁H₁₄O₄	详情	详情
(III)	54907	ethyl (4S,5R)-3-benzoyl-2-oxo-4-phenyl-1,3-oxazolidine-5-carboxylate		C₁₉H₁₇NO₅	详情	详情
(IV)	54908	(2R,3S)-3-amino-2-hydroxy-3-phenylpropanoic acid	136561-53-0	C₉H₁₁NO₃	详情	详情
(V)	31988	(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropionic acid		C₁₆H₁₅NO₄	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

The cyclization of 2(R),3(S)-dihydroxy-3-phenylpropionic acid methyl ester (I) with benzonitrile (II) by means of conc. H2SO4 gives 2,4(S)-diphenyloxazolidine-5(S)-carboxylic acid methyl ester (III). Finally, this compound is submitted to an hydrolytic treatment with aq. H2SO4 to afford the target 3(S)-benzamido-2(R)-hydroxy-3-phenylpropionic acid (IV).

参考文献中间体

合成目标

【1】 Voronkov, M.V.; et al.; Improved large-scale synthesis of phenylisoserine and the taxol C-13 side chain. Tetrahedron Lett 2003, 44, 2, 407.

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)	23889	methyl (2S,3R)-2,3-dihydroxy-3-phenylpropanoate		C₁₀H₁₂O₄	详情	详情
(II)	25904	benzonitrile	100-47-0	C₇H₅N	详情	详情
(III)	61751	methyl (4S,5R)-2,4-diphenyl-4,5-dihydro-1,3-oxazole-5-carboxylate		C₁₇H₁₅NO₃	详情	详情
(IV)	31988	(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropionic acid		C₁₆H₁₅NO₄	详情	详情

Extended Information