(2S,3R)-2-[[(benzyloxy)carbonyl]amino]-3-hydroxybutyric acid -Drug Synthesis Database

【结构式】

【分子编号】43420

【品名】(2S,3R)-2-[[(benzyloxy)carbonyl]amino]-3-hydroxybutyric acid

【CA登记号】19728-63-3

【分子式】C₁₂H₁₅NO₅

【分子量】253.25484

【元素组成】C 56.91% H 5.97% N 5.53% O 31.59%

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：(XII)

For the preparation of tripeptide intermediate (XVIII), N-Cbz-threonine (XII) was coupled with proline benzyl ester (XIII) to give dipeptide (XIV). Subsequent hydrogenolysis of the benzyl groups of (XIV) in the presence of Pd/C furnished threonyl proline (XV). Coupling of (XV) with the succinimidyl ester (XVII) prepared from the protected ornithine (XVI) then provided tripeptide intermediate (XVIII).

参考文献中间体

合成目标

【1】 Chen, H.-J.; Klein, L.L.; Li, L.; et al.; Total synthesis and antifungal evaluation of cyclic aminohexapeptides. Bioorg Med Chem Lett 2000, 8, 7, 1677.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XII)	43420	(2S,3R)-2-[[(benzyloxy)carbonyl]amino]-3-hydroxybutyric acid	19728-63-3	C₁₂H₁₅NO₅	详情	详情
(XIII)	20930	benzyl (2S)-2-pyrrolidinecarboxylate	16652-71-4	C₁₂H₁₅NO₂	详情	详情
(XIV)	43421	benzyl (2S)-1-((2S,3R)-2-[[(benzyloxy)carbonyl]amino]-3-hydroxybutanoyl)-2-pyrrolidinecarboxylate		C₂₄H₂₈N₂O₆	详情	详情
(XV)	43422	(2S)-1-[(2S,3R)-2-amino-3-hydroxybutanoyl]-2-pyrrolidinecarboxylic acid		C₉H₁₆N₂O₄	详情	详情
(XVI)	43423	(2S)-2-[(tert-butoxycarbonyl)amino]-5-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]pentanoic acid		C₂₅H₃₀N₂O₆	详情	详情
(XVII)	43424	9H-fluoren-9-ylmethyl (4S)-4-[(tert-butoxycarbonyl)amino]-5-[(2,5-dioxo-1-pyrrolidinyl)oxy]-5-oxopentylcarbamate		C₂₉H₃₃N₃O₈	详情	详情
(XVIII)	43425	(2S)-1-[(2S,3R)-2-[((2S)-2-[(tert-butoxycarbonyl)amino]-5-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]pentanoyl)amino]-3-hydroxybutanoyl]-2-pyrrolidinecarboxylic acid		C₃₄H₄₄N₄O₉	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The title compound was prepared by two related methods. Norspermidine 1,7-diamide (I) was acylated at the free amino group with N-(benzyloxycarbonyl)-D-threonine (II), yielding triamide (III). The benzyloxycarbonyl protecting group of (III) was then removed by treatment with PdCl2 to give amine (IV). Subsequent methyl ether cleavage to produce the phenolic derivative (V) was carried out using BBr3 in cold CH2Cl2. Then, cyclization of the amino alcohol moiety of threonine derivative (V) with ethyl 2,3-dihydroxybenzimidate (VI) provided the target oxazoline.

参考文献中间体

合成目标

【1】 Bergeron, R.J. Jr. (University of Florida); Synthesis of parabactin and homologs thereof. US 4565874 .

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)	50511	N-[3-([3-[(2,3-dimethoxybenzoyl)amino]propyl]amino)propyl]-2,3-dimethoxybenzamide		C₂₄H₃₃N₃O₆	详情	详情
(II)	43420	(2S,3R)-2-[[(benzyloxy)carbonyl]amino]-3-hydroxybutyric acid	19728-63-3	C₁₂H₁₅NO₅	详情	详情
(III)	50512	benzyl (1R,2S)-1-[(bis[3-[(2,3-dimethoxybenzoyl)amino]propyl]amino)carbonyl]-2-hydroxypropylcarbamate		C₃₆H₄₆N₄O₁₀	详情	详情
(IV)	50513	N-[3-([(2R,3S)-2-amino-3-hydroxybutanoyl][3-[(2,3-dimethoxybenzoyl)amino]propyl]amino)propyl]-2,3-dimethoxybenzamide		C₂₈H₄₀N₄O₈	详情	详情
(V)	50514	N-[3-([(2R,3S)-2-amino-3-hydroxybutanoyl][3-[(2,3-dihydroxybenzoyl)amino]propyl]amino)propyl]-2,3-dihydroxybenzamide		C₂₄H₃₂N₄O₈	详情	详情
(VI)	50515	ethyl 2,3-dihydroxybenzenecarboximidoate		C₉H₁₁NO₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

In an alternative method, 2,3-bis(benzyloxy)benzoic acid (VII) was activated as the corresponding imidazolide (VIII) prior to condensation with norspermidine (IX). The resulting diamide (X) was further acylated with N-(benzyloxycarbonyl)-D-threonine (II) to afford triamide (XI). Hydrogenolysis of the O-benzyl and N-benzyloxycarbonyl protecting groups of (XI) then gave amino alcohol (V), which was finally cyclized with imidate (VI) as above.

参考文献中间体

合成目标

【1】 Bergeron, R.J.; et al.; Significance of asymmetric sites in choosing siderophores as deferration agents. J Med Chem 2001, 44, 15, 2469.
【2】 Bergeron, R.J. Jr. (University of Florida); Synthesis of parabactin and homologs thereof. US 4565874 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	43420	(2S,3R)-2-[[(benzyloxy)carbonyl]amino]-3-hydroxybutyric acid	19728-63-3	C₁₂H₁₅NO₅	详情	详情
(V)	50514	N-[3-([(2R,3S)-2-amino-3-hydroxybutanoyl][3-[(2,3-dihydroxybenzoyl)amino]propyl]amino)propyl]-2,3-dihydroxybenzamide		C₂₄H₃₂N₄O₈	详情	详情
(VI)	50515	ethyl 2,3-dihydroxybenzenecarboximidoate		C₉H₁₁NO₃	详情	详情
(VII)	50516	2,3-bis(benzyloxy)benzoic acid		C₂₁H₁₈O₄	详情	详情
(VIII)	50517	[2,3-bis(benzyloxy)phenyl](1H-imidazol-1-yl)methanone		C₂₄H₂₀N₂O₃	详情	详情
(IX)	50518	Imino bis propylamine; N-(3-Aminopropyl)-1,3-propanediamine; Bis-(3-aminopropyl)amine; Dipropylenetriamine; Dipropylentriamine; 3,3'-Diaminodipropylamine; 3,3'-Iminodipropylamine	56-18-8	C₆H₁₇N₃	详情	详情
(X)	50519	2,3-bis(benzyloxy)-N-[3-[(3-[[2,3-bis(benzyloxy)benzoyl]amino]propyl)amino]propyl]benzamide		C₄₈H₄₉N₃O₆	详情	详情
(XI)	50520	benzyl (1R,2S)-1-[[bis(3-[[2,3-bis(benzyloxy)benzoyl]amino]propyl)amino]carbonyl]-2-hydroxypropylcarbamate		C₆₀H₆₂N₄O₁₀	详情	详情

Extended Information