ethyl (2R,3S)-3-amino-2-hydroxy-3-phenylpropanoate -Drug Synthesis Database

【结构式】

【分子编号】10548

【品名】ethyl (2R,3S)-3-amino-2-hydroxy-3-phenylpropanoate

【CA登记号】

【分子式】C₁₁H₁₅NO₃

【分子量】209.24504

【元素组成】C 63.14% H 7.23% N 6.69% O 22.94%

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：(VI)

3) The condensation of (4S,5R)-3-(bromoacetyl)-4-methyl-5-phenyloxazolidin-2-one (I) with benzaldehyde (II) by means of dibutylboron triflate gives intermediate (III), which by treatment with lithium ethoxide yields (R,R)-3-phenyloxirane-2-carboxylic acid ethyl ester (IV). The reaction of (IV) with sodium azide in ethanol affords the hydroxy ester (V), which is hydrogenated with H2 over Pd/C in ethyl acetate, giving the amino ester (VI). The protection of (VI) with tert-butoxycarbonyl anhydride affords the protected amino ester (VII), which is treated with 2-methoxypropene and pyridinium p-toluenesulfonate to give the oxazolidine (VIII). The hydrolysis of (VIII) with LiOH in ethanol/water yields (4S,5R)-3-(tert-butoxycarbonyl)-2,2-dimethyl-4-phenyloxazolidine-5-carboxylic acid (IX), which is condensed with the protected baccatin III (X) by means of dicyclohexylcarbodiimide (DCC) and DMAP to afford the oxazolidine ester (XI). The treatment of (XI) with formic acid gives the amino ester (XII), which is benzoylated with benzoyl chloride and NaHCO3 to the protected paclitaxel (XIII). Finally, this compound is deprotected by treatment with Zn/acetic acid. (Commercon, A. et al. Tetrahedron Lett 1992, 33(36): 5185).

参考文献中间体

合成目标

【1】 Guy, R.K.; Nicolaou, K.C.; Dai, W.M.; Chemistry and biology of taxol. Angew Chem. Int Ed Engl 1994, 33, 1, 15.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	63033	2-(ethyloxy)-1-propene; ethyl 1-methylethenyl ether		C₅H₁₀O	详情	详情
(I)	10544	(4S,5R)-3-(2-Bromoacetyl)-4-methyl-5-phenyl-1,3-oxazolan-2-one		C₁₂H₁₂BrNO₃	详情	详情
(II)	10498	Benzaldehyde;Benzoic aldehyde;Phenylmethanal	100-52-7	C₇H₆O	详情	详情
(III)	10545	(4S,5R)-3-[(2S,3R)-2-Bromo-3-hydroxy-3-phenylpropanoyl]-4-methyl-5-phenyl-1,3-oxazolan-2-one		C₁₉H₁₈BrNO₄	详情	详情
(IV)	10546	ethyl (2R,3R)-3-phenyl-2-oxiranecarboxylate	121-39-1	C₁₁H₁₂O₃	详情	详情
(V)	10547	ethyl (2R,3S)-3-azido-2-hydroxy-3-phenylpropanoate		C₁₁H₁₃N₃O₃	详情	详情
(VI)	10548	ethyl (2R,3S)-3-amino-2-hydroxy-3-phenylpropanoate		C₁₁H₁₅NO₃	详情	详情
(VII)	10549	ethyl (2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoate		C₁₆H₂₃NO₅	详情	详情
(VIII)	10550	3-(tert-butyl) 5-ethyl (4S,5R)-2,2-dimethyl-4-phenyl-1,3-oxazolidine-3,5-dicarboxylate		C₁₉H₂₇NO₅	详情	详情
(IX)	10551	(4S,5R)-3-(tert-Butoxycarbonyl)-2,2-dimethyl-4-phenyl-1,3-oxazolane-5-carboxylic acid		C₁₇H₂₃NO₅	详情	详情
(X)	10448	(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-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₃₄H₃₉Cl₃O₁₃	详情	详情
(XI)	10553	5-((1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-2-(benzoyloxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-15-yl) 3-(tert-butyl) (4S,5R)-2,2-dimethyl-4-phenyl-1,3-oxazolidine-3,5-dicarboxylate		C₅₁H₆₀Cl₃NO₁₇	详情	详情
(XII)	10554	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-3-amino-2-hydroxy-3-phenylpropanoyl]oxy]-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₄₃H₄₈Cl₃NO₁₅	详情	详情
(XIII)	10555	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-3-amino-2-hydroxy-3-phenylpropanoyl]oxy]-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₄₃H₄₈Cl₃NO₁₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

A partial synthesis of Taxol starting from deacetyl Baccatin III (XI) has been developed: The starting compounds, the acid (I) and the silylated Baccatin III (II) have been obtained as follows: a) The reaction of 3(S)-amino-2(R)-hydroxy-3-phenylpropionic acid ethyl ester (VIII) with benzyloxycarbonyl chloride and Na2CO3 in ethyl or tert-butyl ether/water gives 3(S)-(benzyloxycarbonylamino)-2(R)-hydroxy-3-phenylpropionic acid ethyl ester (IX), which is condensed with benzyloxymethyl chloride by means of BuLi in THF yielding the fully protected ester (X). The hydrolysis of (X) with LiOH in ethanol/water affords the desired acid (I). b) The silylation of (deacetyl Baccatin III) (XI) with triethylsilyl chloride in pyridine gives the monosilylated deacetyl Baccatin III (XII), which is then acetylated with acetyl chloride in pyridine or BuLi in THF to afford the desired silylated Baccatin III (II).

参考文献中间体

合成目标

【1】 Sisti, N.J.; Swindell, C.S.; Chander, M.C. (NaPro BioTherapeutics, Inc.); Paclitaxel synthesis from precursor compounds and methods of producing the same. US 5675025 .

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)	10736	(2R,3S)-3-[[(Benzyloxy)carbonyl]amino]-2-[(benzyloxy)methoxy]-3-phenylpropionic acid		C₂₅H₂₅NO₆	详情	详情
(II)	10737	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,15-dihydroxy-9-methoxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₃₂H₄₀O₁₁	详情	详情
(III)	10738	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-([(2R,3S)-3-[[(benzyloxy)carbonyl]amino]-2-[(benzyloxy)methoxy]-3-phenylpropanoyl]oxy)-1-hydroxy-9-methoxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₅₇H₆₃NO₁₆	详情	详情
(IV)	10739	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-([(2R,3S)-3-amino-2-[(benzyloxy)methoxy]-3-phenylpropanoyl]oxy)-1-hydroxy-9-methoxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₄₉H₅₇NO₁₄	详情	详情
(VIII)	10548	ethyl (2R,3S)-3-amino-2-hydroxy-3-phenylpropanoate		C₁₁H₁₅NO₃	详情	详情
(IX)	10741	ethyl (2R,3S)-3-[[(benzyloxy)carbonyl]amino]-2-hydroxy-3-phenylpropanoate		C₁₉H₂₁NO₅	详情	详情
(X)	10742	ethyl (2R,3S)-3-[[(benzyloxy)carbonyl]amino]-2-[(benzyloxy)methoxy]-3-phenylpropanoate		C₂₇H₂₉NO₆	详情	详情
(XI)	10467	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1,9,12,15-tetrahydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate	32981-86-5	C₂₉H₃₆O₁₀	详情	详情
(XII)	10744	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1,12,15-trihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₃₅H₅₀O₁₀Si	详情	详情

Extended Information