(2R)-2-[(tert-butoxycarbonyl)amino]-3-cyclohexylpropionic acid -Drug Synthesis Database

【结构式】

【分子编号】29348

【品名】(2R)-2-[(tert-butoxycarbonyl)amino]-3-cyclohexylpropionic acid

【CA登记号】

【分子式】C₁₄H₂₅NO₄

【分子量】271.35684

【元素组成】C 61.97% H 9.29% N 5.16% O 23.58%

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)

The title compound was synthesized by stepwise solid-phase peptide synthesis, starting from the protected arginine linked to PAM resin (I). After deprotection of the Boc group of (I) with trifluoroacetic acid, coupling with (Boc)-tryptophan (II) in the presence of TBTU and diisopropylethylamine afforded the dipeptide resin (III). Sequential deprotection and coupling cycles with (Boc)-D-cyclohexylalanine (IV), (Boc)-proline (VI), (Boc)-ornithine (VIII), and (Fmoc)-phenylalanine (X) provided the resins (V), (VII), (IX) and (XI), respectively.

参考文献中间体

合成目标

【1】 Wong, A.K.; Shields, I.A.; Taylor, S.M.; Short, A.; Fairlie, D.P.; Haaima, G.; Finch, A.M.; Effects of a new C5a receptor antagonist on C5a- and endotoxin-induced neutropenia in the rat. Br J Pharmacol 1999, 126, 3, 551.

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)	19064	(2S)-2-[(tert-butoxycarbonyl)amino]-5-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]pentanoic acid		C₁₈H₂₈N₄O₆S	详情	详情
(II)	16114	N-alpha-t-BOC-L-tryptophan; (2S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-indol-3-yl)propionic acid	13139-14-5	C₁₆H₂₀N₂O₄	详情	详情
(III)	29340	(2S)-2-[[(2S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]pentanoic acid		C₂₉H₃₈N₆O₇S	详情	详情
(IV)	29348	(2R)-2-[(tert-butoxycarbonyl)amino]-3-cyclohexylpropionic acid		C₁₄H₂₅NO₄	详情	详情
(V)	29341	(6R,9S,12S)-6-(cyclohexylmethyl)-12-[3-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]propyl]-9-(1H-indol-3-ylmethyl)-2,2-dimethyl-4,7,10-trioxo-3-oxa-5,8,11-triazatridecan-13-oic acid		C₃₈H₅₃N₇O₈S	详情	详情
(VI)	16734	(2S)-1-(tert-butoxycarbonyl)tetrahydro-1H-pyrrole-2-carboxylic acid; N-alpha-t-BOC-L-proline; (2S)-1-(tert-butoxycarbonyl)-2-pyrrolidinecarboxylic acid		C₁₀H₁₇NO₄	详情	详情
(VII)	29342	(2S)-2-[[(2S)-2-[[(2R)-2-([[(2S)-1-(tert-butoxycarbonyl)pyrrolidinyl]carbonyl]amino)-3-cyclohexylpropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]pentanoic acid		C₄₃H₆₀N₈O₉S	详情	详情
(VIII)	29343	(2S)-5-amino-2-[(tert-butoxycarbonyl)amino]pentanoic acid	21887-64-9	C₁₀H₂₀N₂O₄	详情	详情
(IX)	29344	(2S)-2-[[(2S)-2-[((2R)-2-[[((2S)-1-[(2S)-5-amino-2-[(tert-butoxycarbonyl)amino]pentanoyl]pyrrolidinyl)carbonyl]amino]-3-cyclohexylpropanoyl)amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]pentanoic acid		C₄₈H₇₀N₁₀O₁₀S	详情	详情
(X)	19030	(2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-phenylpropionic acid; N-((9H-fluoren-9-ylmethoxy)carbonyl)-phenylalanine	35661-40-6	C₂₄H₂₁NO₄	详情	详情
(XI)	29345	Fluorenylmethoxycarbonyl-L-phenylalanyl-L-ornithyl-L-prolyl-D-cyclohexylalanyl-L-tryptophyl-L-(Nomega-tosyl)arginine		C₆₇H₈₁N₁₁O₁₁S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

The compound was prepared by solid-phase peptide synthesis on a PAM-resin. Starting from a N(alpha)-Boc-N(gamma)-Tos-L-arginine resin (I), cleavage of the Boc protecting group by means of trifluoroacetic acid provided Arg(Tos)-resin (II). Coupling of (II) with N(alpha)-Boc-L-tryptophan (III) using O-benzotriazol-1-yl-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU) and diisopropylethylamine, followed by acid cleavage of the Boc group gave dipeptide resin (IV). This was in turn coupled and deprotected with the following amino acids N-Boc-D-cyclohexylalanine (V), N--Boc-L-proline (VII) and N(alpha)-Boc-N(delta)-Tos-L-ornithine (IX) to furnish the peptide resins (VI), (VIII), (X) and (XII), respectively.

参考文献中间体

合成目标

【1】 Wong, A.K.; Finch, A.M.; Pierens, G.K.; Craik, D.J.; Taylor, S.M.; Fairlie, D.P.; Small molecular probes for G-protein-coupled C5a receptors: Conformationally constrained antagonists derived from the C terminus of the human plasma protein C5a. J Med Chem 1998, 41, 18, 3417.
【2】 Wong, A.K.; Fairlie, D.P.; Finch, A.M.; Wadi, S.K.; Craik, D.J.; Taylor, S.M.; Paczkowski, N.J.; Low-molecular-weight peptidic and cyclic antagonists of the receptor for the complement factor C5a. J Med Chem 1999, 42, 11, 1965.
【3】 Fairlie, D.; Wong, A.; Finch, A.M.; Taylor, S.M. (University of Queensland); Cyclic agonists and antagonists of C5a receptors and G protein-coupled receptors. EP 1017713; WO 9900406 .

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)	19064	(2S)-2-[(tert-butoxycarbonyl)amino]-5-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]pentanoic acid		C₁₈H₂₈N₄O₆S	详情	详情
(II)	34498	(2S)-2-amino-5-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]pentanoic acid		C₁₃H₂₀N₄O₄S	详情	详情
(III)	16114	N-alpha-t-BOC-L-tryptophan; (2S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-indol-3-yl)propionic acid	13139-14-5	C₁₆H₂₀N₂O₄	详情	详情
(IV)	34499	(2S)-2-[[(2S)-2-amino-3-(1H-indol-3-yl)propanoyl]amino]-5-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]pentanoic acid		C₂₄H₃₀N₆O₅S	详情	详情
(V)	29348	(2R)-2-[(tert-butoxycarbonyl)amino]-3-cyclohexylpropionic acid		C₁₄H₂₅NO₄	详情	详情
(VI)	34500	(2S)-2-[[(2S)-2-[[(2R)-2-amino-3-cyclohexylpropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]pentanoic acid		C₃₃H₄₅N₇O₆S	详情	详情
(VII)	16734	(2S)-1-(tert-butoxycarbonyl)tetrahydro-1H-pyrrole-2-carboxylic acid; N-alpha-t-BOC-L-proline; (2S)-1-(tert-butoxycarbonyl)-2-pyrrolidinecarboxylic acid		C₁₀H₁₇NO₄	详情	详情
(VIII)	34505	(2S)-2-[[(2S)-2-[((2R)-3-cyclohexyl-2-[[(2S)pyrrolidinylcarbonyl]amino]propanoyl)amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]pentanoic acid		C₃₈H₅₂N₈O₇S	详情	详情
(IX)	34501	(2S)-2-[(tert-butoxycarbonyl)amino]-5-[[(4-methylphenyl)sulfonyl]amino]pentanoic acid		C₁₇H₂₆N₂O₆S	详情	详情
(X)	34502			C₅₀H₆₈N₁₀O₁₀S₂	详情	详情

Extended Information