Fluorenylmethoxycarbonyl-L-phenylalanyl-L-ornithyl-L-prolyl-D-cyclohexylalanyl-L-tryptophyl-L-(Nomega-tosyl)arginine -Drug Synthesis Database

【结构式】

【分子编号】29345

【品名】Fluorenylmethoxycarbonyl-L-phenylalanyl-L-ornithyl-L-prolyl-D-cyclohexylalanyl-L-tryptophyl-L-(Nomega-tosyl)arginine

【CA登记号】

【分子式】C₆₇H₈₁N₁₁O₁₁S

【分子量】1248.51368

【元素组成】C 64.46% H 6.54% N 12.34% O 14.1% S 2.57%

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：(XI)

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：(XI)

Cleavage from the resin (XI) using anhydrous HF in the presence of thiocresol furnished the linear peptide (XII). This was cyclized employing BOP and diisopropylethylamine in DMF to give the cyclic peptide (XIII). The Fmoc group of (XIII) was finally deprotected by means of piperidine in DMF.

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	分子式	供应商	用于合成
(XI)	29345	Fluorenylmethoxycarbonyl-L-phenylalanyl-L-ornithyl-L-prolyl-D-cyclohexylalanyl-L-tryptophyl-L-(Nomega-tosyl)arginine	C₆₇H₈₁N₁₁O₁₁S	详情	详情
(XII)	29346	N-(Fluoren-9-ylmethoxycarbonyl)-L-phenylalanyl-L-ornithyl-L-prolyl-L-cyclohexylalanyl-L-tryptophyl-L-arginine	C₆₀H₇₅N₁₁O₉	详情	详情
(XIII)	29347	N-(Fluoren-9-ylmethoxycarbonyl)-L-phenylalanyl-L-ornithyl-L-prolyl-L-cyclohexylalanyl-L-tryptophyl-L-arginine C-1,6-N-5,2 cyclic lactam	C₆₀H₇₃N₁₁O₈	详情	详情

Extended Information