N-(tert-butoxycarbonyl)alanine -Drug Synthesis Database

【结构式】

【分子编号】20337

【品名】N-(tert-butoxycarbonyl)alanine

【CA登记号】

【分子式】C₈H₁₅NO₄

【分子量】189.21144

【元素组成】C 50.78% H 7.99% N 7.4% O 33.82%

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：(IV)

1) The esterification of 7-[(R)-mandelamido]-3-(5-methyl-1,3,4-thiadiazol-2-ylthiomethyl)-3-cephem-4-carboxylic acid (KY-087; I) with 4-bromomethyl-5-methyl-1,3-dioxol-2-one (II) by means of potassium acetate in DMF gives the corresponding ester (KY-106; III), which is condensed with tert-butoxycarbonyl-L-alanine (IV) by means of dicyclohexylcarbodiimide (DCC) and 4-(dimethylamino)pyridine (DMP) in dichloromethane affording the protected final product (V). Finally, this compound is deprotected with HCl in methanol-acetone.

参考文献中间体

合成目标

【1】 Kaneya, N.; Nishizawa, S.; Tamaki, S.; Kitao, K. (Kyoto Pharmaceutical Industries, Ltd.); Antibiotic amino acid derivatives of cephalosporins.. JP 59116292; US 4605651; WO 8401949 .
【2】 Kakeya, N.; Nishizawa, S.; Nishimura, K.; Yoshimi, A.; Tamaki, S.; Mori, T.; Kitao, K.; KY-109, A new bifunctional pro-drug of a cephalosporin. Chemistry, physico-chemical and biological properties. J Antibiot 1985, 38, 3, 380-9.
【3】 Prous, J.; Castaner, J.; CEFCANEL DALOXATE HYDROCHLORIDE < Prop INNM >. Drugs Fut 1989, 14, 1, 13.

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)	20334	(7R)-7-[[2-(2-hydroxyphenyl)acetyl]amino]-3-[[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid		C₁₉H₁₈N₄O₅S₃	详情	详情
(II)	13462	4-(Bromomethyl)-5-methyl-1,3-dioxol-2-one	80715-22-6	C₅H₅BrO₃	详情	详情
(III)	20336	(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (7R)-7-[[(2R)-2-hydroxy-2-phenylethanoyl]amino]-3-[[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₂₄H₂₂N₄O₈S₃	详情	详情
(IV)	20337	N-(tert-butoxycarbonyl)alanine		C₈H₁₅NO₄	详情	详情
(V)	20338	(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (7R)-7-[[(2R)-2-([2-[(tert-butoxycarbonyl)amino]propanoyl]oxy)-2-phenylethanoyl]amino]-3-[[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₃₂H₃₅N₅O₁₁S₃	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 condensation of tert-butoxycarbonyl-L-alanine (I) with benzyl D-isoglutaminate (II) by means of N-hydroxysuccinimide (NOHS) and dicyclohexylcarbodiimide (DCC) gives the protected dipeptide (III), which is hydrogenated with H2 over Pd/C in methanol yielding tert-butoxycarbonyl-D-isoglutaminyl-L-alanine (IV). The condensation of (IV) with Nepsilon-(benzyloxycarbonyl)-L-lysine benzyl ester (V) by means of ethyl chloroformate and triethylamine affords the protected tripeptide (VI), which is treated with trifluoroacetic acid (TFA) to afford L-alanyl-D-isoglutaminyl-(Nepsilon-benzyloxycarbonyl)-L-lysine benzyl ester (VII).

参考文献中间体

合成目标

【1】 Shiba, T.; Yamamura, Y.; Nagase, O.; Kotani, S.; Ogawa, H. (Daiichi Seiyaku Co.; Ltd.); Muramyldipeptide derivatives, process for preparing said compounds and pharmaceutical compositions containing said compounds. EP 0021367 .
【2】 Robinson, C.P.; MUROCTASIN. Drugs Fut 1989, 14, 5, 432.
【3】 Shiba, T.; Kusumoto, S.; Tarumi, Y.; Ikenaka, K.; Chemical synthesis of N-acetylmuramyl peptides with partial structures of bacterial cell wall and their analogs in relation to immunoadjuvant activities. 1976, 49(2): 533-9. Bull Chem Soc Jpn 1976, 49, 2, 533.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	20337	N-(tert-butoxycarbonyl)alanine	C₈H₁₅NO₄	详情	详情
(II)	20868	benzyl 4,5-diamino-5-oxopentanoate	C₁₂H₁₆N₂O₃	详情	详情
(III)	20869	benzyl 5-amino-4-([2-[(tert-butoxycarbonyl)amino]propanoyl]amino)-5-oxopentanoate	C₂₀H₂₉N₃O₆	详情	详情
(IV)	20870	5-amino-4-([2-[(tert-butoxycarbonyl)amino]propanoyl]amino)-5-oxopentanoic acid	C₁₃H₂₃N₃O₆	详情	详情
(V)	20871	benzyl 2-amino-6-[[(benzyloxy)carbonyl]amino]hexanoate	C₂₁H₂₆N₂O₄	详情	详情
(VI)	20872	benzyl 9-(aminocarbonyl)-14-(4-[[(benzyloxy)carbonyl]amino]butyl)-2,2,6-trimethyl-4,7,12-trioxo-3-oxa-5,8,13-triazapentadecan-15-oate	C₃₄H₄₇N₅O₉	详情	详情
(VII)	20873	benzyl 2-([5-amino-4-[(2-aminopropanoyl)amino]-5-oxopentanoyl]amino)-6-[[(benzyloxy)carbonyl]amino]hexanoate	C₂₉H₃₉N₅O₇	详情	详情

Extended Information