(S)-(-)-2-Chloropropionic acid; (S)-2-Chloropropionic acid -Drug Synthesis Database

【结构式】

【分子编号】56332

【品名】(S)-(-)-2-Chloropropionic acid; (S)-2-Chloropropionic acid

【CA登记号】29617-66-1

【分子式】C₃H₅ClO₂

【分子量】108.5242

【元素组成】C 33.2% H 4.64% Cl 32.67% O 29.49%

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：(XI)

Alkylation of the sodium alkoxide of (X) with (S)-2-chloropropionic acid (XI), followed by esterification with diazomethane provided the methyl ester adduct (XII). Alkaline hydrolysis of ester (XII) with KOH yielded carboxylic acid (XIII), which was coupled with the dipeptide amide (XIV) to give the protected disaccharide dipeptide (XV). Subsequent acidic hydrolysis of the ketal functions of (XV) proceeded with concomitant cyclization to the pyranose form (XVI). The O-benzyl protecting groups of (XVI) were finally removed by catalytic hydrogenolysis in the presence of palladium black.

参考文献中间体

合成目标

【1】 Kusumoto, S.; et al.; Synthesis of N-acetyl-beta-D-glucosaminyl-(1-4)-N-acetylmuramyl-L-alanyl-D-isoglutamine. Tetrahedron Lett 1978, 45, 4407.
【2】 Kusumoto, S.; et al.; Chemical synthesis and biological activities of two disaccharide dipeptides corresponding to the repeating units of bacterial peptidoglycan. Bull Chem Soc Jpn 1986, 59, 5, 1411.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(X)	56331	N-{(1R,2R,3S)-3-({(2S,3R,4R,5S,6R)-3-(acetylamino)-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl}oxy)-1-(diethoxymethyl)-3-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-hydroxypropyl}acetamide		C₄₄H₆₀N₂O₁₂	详情	详情
(XI)	56332	(S)-(-)-2-Chloropropionic acid; (S)-2-Chloropropionic acid	29617-66-1	C₃H₅ClO₂	详情	详情
(XII)	56333	methyl (2R)-2-[((1R,2R)-2-(acetylamino)-1-{(S)-({(2S,3R,4R,5S,6R)-3-(acetylamino)-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl}oxy)[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-3,3-diethoxypropyl)oxy]propanoate		C₄₈H₆₆N₂O₁₄	详情	详情
(XIII)	56334	(2R)-2-[((1R,2R)-2-(acetylamino)-1-{(S)-({(2S,3R,4R,5S,6R)-3-(acetylamino)-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl}oxy)[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-3,3-diethoxypropyl)oxy]propanoic acid		C₄₇H₆₄N₂O₁₄	详情	详情
(XIV)	27130	benzyl (4R)-5-amino-4-[[(2S)-2-aminopropanoyl]amino]-5-oxopentanoate		C₁₅H₂₁N₃O₄	详情	详情
(XV)	56335	benzyl (5R,6R,8R,11S,14R)-5-(acetylamino)-6-{(S)-({(2S,3R,4R,5S,6R)-3-(acetylamino)-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl}oxy)[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-14-(aminocarbonyl)-4-ethoxy-8,11-dimethyl-9,12-dioxo-3,7-dioxa-10,13-diazaheptadecan-17-oate		C₆₂H₈₃N₅O₁₇	详情	详情
(XVI)	56336	benzyl (4R)-4-({(2S)-2-[((2R)-2-{[(2S,3R,4R,5S,6R)-3-(acetylamino)-5-({(2S,3R,4R,5S,6R)-3-(acetylamino)-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl}oxy)-2-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-4-yl]oxy}propanoyl)amino]propanoyl}amino)-5-amino-5-oxopentanoate		C₅₅H₆₉N₅O₁₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XI)

Glycosylation of the protected glucosamine (XXVI) with the glucopyranooxazoline (XXVII) was effected in the presence of p-toluenesulfonic acid in dichloroethane to give the protected chitobioside derivative (XXVIII). Methanolysis of the acetate esters of (XXVIII), followed by protection of the resultant triol (XXIX) with acetone dimethylacetal, gave rise to the 4',6'-isopropylidene derivative (XXX). The 3'-hydroxyl group of (XXX) was then protected as the benzyl ether (XXXI) with benzyl bromide in the presence of Ba(OH)2 and BaO. Removal of the 2-butenyl group of (XXXI) to furnish (XXXII) was performed by means of potassium tert-butoxide in hot DMSO. Subsequent alkylation of (XXXII) with (S)-2-chloropropionic acid (XI) led to acid (XXXIII).

参考文献中间体

合成目标

【1】 Kiso, M.; et al.; A general, convenient synthesis of the repeating, disaccharide-dipeptide unit of the bacterial, cell-wall peptidoglycan by the oxazoline method. Carbohydr Res 1980, 83, 1, C8.
【2】 Kiso, M.; et al.; Synthesis and immunoadjuvant activities of the repeating, disaccharide-dipeptide unit of the bacterial, cell-wall peptidoglycan and of some carbohydrate analogs. Carbohydr Res 1982, 104, 2, 253.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XI)	56332	(S)-(-)-2-Chloropropionic acid; (S)-2-Chloropropionic acid	29617-66-1	C₃H₅ClO₂	详情	详情
(XXVI)	56344	N-{(2S,3R,4R,5S,6R)-2-(benzyloxy)-6-[(benzyloxy)methyl]-4-[(E)-2-butenyloxy]-5-hydroxytetrahydro-2H-pyran-3-yl}acetamide		C₂₆H₃₃NO₆	详情	详情
(XXVII)	21969	(3aR,5R,6R,7R,7aR)-6-(acetoxy)-5-[(acetoxy)methyl]-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d][1,3]oxazol-7-yl acetate		C₁₄H₁₉NO₈	详情	详情
(XXVIII)	56345	(2R,3R,4R,5R,6R)-3-(acetylamino)-2-({(2R,3S,4R,5R,6S)-5-(acetylamino)-6-(benzyloxy)-2-[(benzyloxy)methyl]-4-[(E)-2-butenyloxy]tetrahydro-2H-pyran-3-yl}oxy)-5-(acetyloxy)-6-[(acetyloxy)methyl]tetrahydro-2H-pyran-4-yl acetate		C₄₀H₅₂N₂O₁₄	详情	详情
(XXIX)	56346	N-[(2S,3R,4R,5S,6R)-2-({(2R,3S,4R,5R,6S)-5-(acetylamino)-6-(benzyloxy)-2-[(benzyloxy)methyl]-4-[(E)-2-butenyloxy]tetrahydro-2H-pyran-3-yl}oxy)-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl]acetamide		C₃₄H₄₆N₂O₁₁	详情	详情
(XXX)	56347	N-[(4aR,6R,7R,8R,8aS)-6-({(2R,3S,4R,5R,6S)-5-(acetylamino)-6-(benzyloxy)-2-[(benzyloxy)methyl]-4-[(E)-2-butenyloxy]tetrahydro-2H-pyran-3-yl}oxy)-8-hydroxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-7-yl]acetamide		C₃₇H₅₀N₂O₁₁	详情	详情
(XXXI)	56348	N-[(4aR,6R,7R,8R,8aS)-6-({(2R,3S,4R,5R,6S)-5-(acetylamino)-6-(benzyloxy)-2-[(benzyloxy)methyl]-4-[(E)-2-butenyloxy]tetrahydro-2H-pyran-3-yl}oxy)-8-(benzyloxy)-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-7-yl]acetamide		C₄₄H₅₆N₂O₁₁	详情	详情
(XXXII)	56349	N-[(4aR,6R,7R,8R,8aS)-6-({(2R,3S,4R,5R,6S)-5-(acetylamino)-6-(benzyloxy)-2-[(benzyloxy)methyl]-4-hydroxytetrahydro-2H-pyran-3-yl}oxy)-8-(benzyloxy)-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-7-yl]acetamide		C₄₀H₅₀N₂O₁₁	详情	详情
(XXXIII)	56350	(2R)-2-({(2R,3S,4R,5R,6S)-3-{[(4aR,6R,7R,8R,8aS)-7-(acetylamino)-8-(benzyloxy)-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy}-5-(acetylamino)-6-(benzyloxy)-2-[(benzyloxy)methyl]tetrahydro-2H-pyran-4-yl}oxy)propanoic acid		C₄₃H₅₄N₂O₁₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XI)

Alkylation of (XLVI) with (S)-2-chloropropionic acid (XI) provided the lactic acid derivative (XLVII). This was subsequently coupled with the dipeptide amide (XIV), via activation as the mixed anhydride with isobutyl chloroformate, to give the protected disaccharide dipeptide (XLVIII). Finally, hydrogenolysis of the O-benzyl protecting groups of (XLVIII) in the presence of palladium black led to the title compound.

参考文献中间体

合成目标

【1】 Durette, P.L.; et al.; Synthesis of O-(2-acetamido-2-deoxy-beta-D-glucosyl)-(1--4)-N-acetylmuramoyl-L-alanyl-D-isoglutamine, the repeating disaccharide-dipeptide unit of the bacterial cell-wall peptidoglycan. Carbohydr Res 1979, 77, C1.
【2】 Durette, P.L.; Shen, T.-Y. (Merck & Co., Inc.); Immunologically active peptidyl disaccharides, methods of preparation and vaccine. EP 0018901 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XI)	56332	(S)-(-)-2-Chloropropionic acid; (S)-2-Chloropropionic acid	29617-66-1	C₃H₅ClO₂	详情	详情
(XIV)	27130	benzyl (4R)-5-amino-4-[[(2S)-2-aminopropanoyl]amino]-5-oxopentanoate		C₁₅H₂₁N₃O₄	详情	详情
(XLVI)	56363	N-{(2S,3R,4R,5S,6R)-2-({(2R,3S,4R,5R,6S)-5-(acetylamino)-6-(benzyloxy)-2-[(benzyloxy)methyl]-4-hydroxytetrahydro-2H-pyran-3-yl}oxy)-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-3-yl}acetamide		C₅₁H₅₈N₂O₁₁	详情	详情
(XLVII)	56364	(2R)-2-({(2S,3R,4R,5S,6R)-3-(acetylamino)-5-({(2S,3R,4R,5S,6R)-3-(acetylamino)-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl}oxy)-2-(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-4-yl}oxy)propanoic acid		C₅₄H₆₂N₂O₁₃	详情	详情
(XLVIII)	56365	benzyl (4R)-4-[((2S)-2-{[(2R)-2-({(2S,3R,4R,5S,6R)-3-(acetylamino)-5-({(2S,3R,4R,5S,6R)-3-(acetylamino)-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl}oxy)-2-(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-4-yl}oxy)propanoyl]amino}propanoyl)amino]-5-amino-5-oxopentanoate		C₆₉H₈₁N₅O₁₆	详情	详情

Extended Information