(2R,3R)-3-phenyl-2-oxiranecarboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】23891

【品名】(2R,3R)-3-phenyl-2-oxiranecarboxylic acid

【CA登记号】

【分子式】C₉H₈O₃

【分子量】164.16072

【元素组成】C 65.85% H 4.91% O 29.24%

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：(III)

The reaction of baccatine III (I) with trichloroacetyl chloride in pyridine gives 7-O-(trichloroacetyl)baccatine III (II), which is condensed with 2,3-epoxy-3-phenylpropionic acid (III) by means of DCC and DMAP in toluene to yield the ester (IV). Opening of the epoxide ring of (IV) by means of sodium azide and methyl formate in methanol affords the expected hydroxy azide (V), which is reduced with PPh3 in dichloromethane/water to provide the corresponding amino derivative (VI). Finally, the amino group of (VI) is benzoylated with benzoyl chloride (VII) and NaHCO3 in ethyl acetate/water to furnish the target paclitaxel.

参考文献中间体

合成目标

【1】 Bombardelli, E.; Pontiroli, A.; Battaglia, A.; Dambruoso, P.; Guerrini, A. (Indena SpA); A process for the preparation of paclitaxel. WO 0246177 .

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)	10447	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,9,15-trihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₃₁H₃₈O₁₁	详情	详情
(II)	38901	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(2,2,2-trichloroacetyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₃₃H₃₇Cl₃O₁₂	详情	详情
(III)	23891	(2R,3R)-3-phenyl-2-oxiranecarboxylic acid		C₉H₈O₃	详情	详情
(IV)	54903	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-2-(benzoyloxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(2,2,2-trichloroacetyl)oxy]-6-oxatetracyclo[11.3.1.0~3,10~.0~4,7~]heptadec-13-en-15-yl (2R,3R)-3-phenyl-2-oxiranecarboxylate		C₄₂H₄₃Cl₃O₁₄	详情	详情
(V)	54904	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-{[(2R,3S)-3-azido-2-hydroxy-3-phenylpropanoyl]oxy}-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0~3,10~.0~4,7~]heptadec-13-en-2-yl benzoate		C₄₀H₄₅N₃O₁₃	详情	详情
(VI)	10729	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-3-amino-2-hydroxy-3-phenylpropanoyl]oxy]-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₄₀H₄₇NO₁₃	详情	详情
(VII)	10463	Benzoyl chloride	98-88-4	C₇H₅ClO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

A new synthesis of docetaxel has been developed: The stereoselective dihydroxylation of methyl cinnamate (I) by the Sharpless AD process gives the enantiopure diol (II), which was treated first with tosyl chloride/triethylamine and then with K2CO3 in DMF yielding epoxide (III). Hydrolysis of the ester group of (III) with LiOH in methanol/water affords the epoxy-acid (IV), which is coupled with 7,10-bis(2,2,2-trichloroethoxycarbonyl)-10-deacetylbaccatin III (V) by means of dicyclohexylcarbodiimide (CDD) and dimethylaminopyridine in hot toluene to give the ester (VI). Regioselective cleavage of the epoxide ring of (VI) with NaN3 in aqueous methanol yielded the azide derivative (VII), which was treated with triphenylphosphine in the presence of tert-butoxycarbonyl anhydride and K2CO3 in dichloromethane affording the tert-butoxycarbonylamino derivative (VIII). Finally, (VIII) was submitted to a reductive deprotection with zinc powder in acetic acid.

参考文献中间体

合成目标

【1】 Harada, N.; Yamaguchi, T.; Hashiyama, T.; Ozaki, K.; Synthesis of taxoids 3. A novel and efficient method for preparation of taxoids employing cis-glycidic acid. Tetrahedron Lett 1998, 39, 5575.

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)	23888	methyl (E)-3-phenyl-2-propenoate	103-26-4	C₁₀H₁₀O₂	详情	详情
(II)	23889	methyl (2S,3R)-2,3-dihydroxy-3-phenylpropanoate		C₁₀H₁₂O₄	详情	详情
(III)	23890	methyl (2R,3R)-3-phenyl-2-oxiranecarboxylate	99528-65-1	C₁₀H₁₀O₃	详情	详情
(IV)	23891	(2R,3R)-3-phenyl-2-oxiranecarboxylic acid		C₉H₈O₃	详情	详情
(V)	23892	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9,12-bis[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₃₅H₃₈Cl₆O₁₄	详情	详情
(VI)	23893	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-2-(benzoyloxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9,12-bis[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-15-yl (2R,3R)-3-phenyl-2-oxiranecarboxylate		C₄₄H₄₄Cl₆O₁₆	详情	详情
(VII)	23894	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-15-[[(2R,3S)-3-azido-2-hydroxy-3-phenylpropanoyl]oxy]-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9,12-bis[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl ben		C₄₄H₄₅Cl₆N₃O₁₆	详情	详情
(VIII)	23895	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-15-([(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoyl]oxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9,12-bis[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]		C₄₉H₅₅Cl₆NO₁₈	详情	详情

Extended Information