(2S)-2-[(tert-butoxycarbonyl)amino]-3-(1-formyl-1H-indol-3-yl)propionic acid -Drug Synthesis Database

【结构式】

【分子编号】25478

【品名】(2S)-2-[(tert-butoxycarbonyl)amino]-3-(1-formyl-1H-indol-3-yl)propionic acid

【CA登记号】

【分子式】C₁₇H₂₀N₂O₅

【分子量】332.35628

【元素组成】C 61.44% H 6.07% N 8.43% O 24.07%

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：(VI)

The solid phase method for the synthesis of peptides is here used starting with a phenylacetamidomethyl resin coupled with boc-protected-L-leucine (I), which was coupled successively with protected L-2,3-diaminopropionic acid (II) yielding dipeptide (III), with protected L-phenylalanine (IV), yielding tripeptide (V), with protected L-tryptophan (VI) yielding tetrapeptide (VII), and with protected L-aspartic acid (VIII), yielding pentapeptide (IX). The cyclization of (IX) by selective deprotection of the side chains of diaminopropionic acid and aspartic acid with piperidine in DMF, followed by cyclization by means of PyBop and DIEA in DMF affords the cyclic pentapeptide (X).

参考文献中间体

合成目标

【1】 Lombardi, A.; D'Agostino, B.; Filippelli, A.; Pedone, C.; Matera, M.G.; Falciani, M.; De Rosa, M.; Rossi, F.; Pavone, V.; Neuronorm is a potent and water soluble neurokinin A receptor antagonist. Bioorg Med Chem Lett 1998, 8, 13, 1735.

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)	26057	L-Leucine	61-90-5	C₆H₁₃NO₂	详情	详情
(II)	27439	(2S)-2-[(tert-butoxycarbonyl)amino]-3-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]propionic acid		C₂₃H₂₆N₂O₆	详情	详情
(III)	27440	(2S)-2-[((2S)-2-[(tert-butoxycarbonyl)amino]-3-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]propanoyl)amino]-4-methylpentanoic acid		C₂₉H₃₇N₃O₇	详情	详情
(IV)	12874	(2R)-2-[(tert-Butoxycarbonyl)amino]-3-phenylpropionic acid; N-alpha-t-BOC-L-Phenylalanine	13734-34-4	C₁₄H₁₉NO₄	详情	详情
(V)	27441	(6S,9S,12S)-6-benzyl-9-([[(9H-fluoren-9-ylmethoxy)carbonyl]amino]methyl)-12-isobutyl-2,2-dimethyl-4,7,10-trioxo-3-oxa-5,8,11-triazatridecan-13-oic acid		C₃₈H₄₆N₄O₈	详情	详情
(VI)	25478	(2S)-2-[(tert-butoxycarbonyl)amino]-3-(1-formyl-1H-indol-3-yl)propionic acid		C₁₇H₂₀N₂O₅	详情	详情
(VII)	27442	(6S,9S,12S,15S)-9-benzyl-12-([[(9H-fluoren-9-ylmethoxy)carbonyl]amino]methyl)-6-[(1-formyl-1H-indol-3-yl)methyl]-15-isobutyl-2,2-dimethyl-4,7,10,13-tetraoxo-3-oxa-5,8,11,14-tetraazahexadecan-16-oic acid		C₅₀H₅₆N₆O₁₀	详情	详情
(VIII)	27443	(2S)-2-[(tert-butoxycarbonyl)amino]-4-(9H-fluoren-9-ylmethoxy)-4-oxobutyric acid		C₂₃H₂₅NO₆	详情	详情
(IX)	27444	(6S,9S,12S,15S,18S)-12-benzyl-15-([[(9H-fluoren-9-ylmethoxy)carbonyl]amino]methyl)-6-[2-(9H-fluoren-9-ylmethoxy)-2-oxoethyl]-9-[(1-formyl-1H-indol-3-yl)methyl]-18-isobutyl-2,2-dimethyl-4,7,10,13,16-pentaoxo-3-oxa-5,8,11,14,17-pentaazanonadecan-19-oic acid		C₆₈H₇₁N₇O₁₃	详情	详情
(X)	27445	(2S)-2-([[(3S,6S,9S,12S)-6-benzyl-12-[(tert-butoxycarbonyl)amino]-9-(1H-indol-3-ylmethyl)-5,8,11,14-tetraoxo-1,4,7,10-tetraazacyclotetradecan-3-yl]carbonyl]amino)-4-methylpentanoic acid		C₃₈H₄₉N₇O₉	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The peptide was synthesized by a solid-phase method using a p-methylbenzhydrylamine resin to which N1-Boc-N6-Fmoc-L-lysine (I) was coupled giving (II). To this solid phase the following protected amino acids Nalpha-Boc-N1-formyl-L-tryptophan (III), Nalpha-Boc-Nomega-Tos-L-arginine (V), Nalpha-Boc-D-(2-naphthyl)alanine (VII), Nalpha-Boc-Npi-L-histidine (IX) and Nalpha-Boc-Ogamma-Fm-L-aspartic acid (XI) were sequentially coupled yielding resins (IV), (VI), (VIII), (X) and (XII).

参考文献中间体

合成目标

【1】 Al-Obeidi, F.A.; Sharma, S.D.; de L. Castrucci, A.; Kesterson, R.A.; Lu, D.; Hadley, M.E.; Cone, R.D.; Hruby, V.J.; Cyclic lactam alpha-melanotropin analogues of Ac-Nle4-cyclo[Asp5, D-Phe7,Lys10] alpha-melanocyte-stimulating hormone-(4-10)-NH2 with bulky aromatic amino acids at position 7 show high antagonist potency and selectivity at specific melanocortin receptors. J Med Chem 1995, 38, 18, 3454.
【2】 Hadley, M.E.; Hruby, V.J.; Sharma, S.D. (University of Arizona); Peptides having potent antagonist and agonist bioactivities at melanocortin receptors. US 5731408 .

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)	25476	(2S)-2-[(tert-butoxycarbonyl)amino]-6-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]hexanoic acid	84624-27-1	C₂₆H₃₂N₂O₆	详情	详情
(II)	25477	9H-fluoren-9-ylmethyl (5S)-6-amino-5-[(tert-butoxycarbonyl)amino]-6-oxohexylcarbamate		C₂₆H₃₃N₃O₅	详情	详情
(III)	25478	(2S)-2-[(tert-butoxycarbonyl)amino]-3-(1-formyl-1H-indol-3-yl)propionic acid		C₁₇H₂₀N₂O₅	详情	详情
(IV)	25479	9H-fluoren-9-ylmethyl (5S)-6-amino-5-[[(2S)-2-[(tert-butoxycarbonyl)amino]-3-(1-formyl-1H-indol-3-yl)propanoyl]amino]-6-oxohexylcarbamate		C₃₈H₄₃N₅O₇	详情	详情
(V)	19064	(2S)-2-[(tert-butoxycarbonyl)amino]-5-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]pentanoic acid		C₁₈H₂₈N₄O₆S	详情	详情
(VI)	25480	tert-butyl (1S,4S,7S)-7-(aminocarbonyl)-15-(9H-fluoren-9-yl)-4-[(1-formyl-1H-indol-3-yl)methyl]-1-[3-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]propyl]-2,5,13-trioxo-14-oxa-3,6,12-triazapentadec-1-ylcarbamate		C₅₁H₆₁N₉O₁₀S	详情	详情
(VII)	23498	(2R)-2-[(tert-butoxycarbonyl)amino]-3-(2-naphthyl)propionic acid		C₁₈H₂₁NO₄	详情	详情
(VIII)	25481	tert-butyl (1R,4S,7S,10S)-10-(aminocarbonyl)-18-(9H-fluoren-9-yl)-7-[(1-formyl-1H-indol-3-yl)methyl]-4-[3-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]propyl]-1-(2-naphthylmethyl)-2,5,8,16-tetraoxo-17-oxa-3,6,9,15-tetraazaoctadec-1-ylcarbamate		C₆₄H₇₂N₁₀O₁₁S	详情	详情
(IX)	25482	(2S)-3-[1-[(benzyloxy)methyl]-1H-imidazol-5-yl]-2-[(tert-butoxycarbonyl)amino]propionic acid	83468-83-1	C₁₉H₂₅N₃O₅	详情	详情
(X)	25483	9H-fluoren-9-ylmethyl (5S,8S,11S,14R,17S)-17-amino-5-(aminocarbonyl)-18-[1-[(benzyloxy)methyl]-1H-imidazol-5-yl]-8-[(1-formyl-1H-indol-3-yl)methyl]-11-[3-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]propyl]-14-(2-naphthylmethyl)-7,10,13,16-tetraoxo-6,9,12,15-tetraazaoctadec-1-ylcarbamate		C₇₃H₇₉N₁₃O₁₁S	详情	详情
(XI)	25484	(2S)-2-[(tert-butoxycarbonyl)amino]-4-[[(9H-fluoren-9-ylmethoxy)carbonyl]oxy]-4-oxobutyric acid		C₂₄H₂₅NO₈	详情	详情
(XII)	25485	N-(Tert-butoxycarbonyl)-[4-O-(9-fluorenylmethoxycarbonyl)]-L-aspartyl-[N-tau-(benzyloxymethyl)]-D-histidyl-D-2-naphthylalanyl-(N-omega-tosyl)-L-arginyl-(N-1-formyl)-D-tryptophyl-[N-6-(9-fluorenylmethoxycarbonyl)]-L-leucinamide; N-(Tert-butoxycarbonyl)-[4-O-(9-fluorenylmethoxycarbonyl)]-L-aspartyl-[N-tau-(benzyloxymethyl)]-D-histidyl-D-2-naphthylalanyl-(N-omega-tosyl)-L-arginyl-(N-1-formyl)-D-tryptophyl-[N-6-(9-fluorenylmethoxycarbonyl)]-L-leucinamide		C₉₇H₁₀₂N₁₄O₁₈S	详情	详情

Extended Information