(2S,3R)-3-(tert-butoxy)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]butyric acid -Drug Synthesis Database

【结构式】

【分子编号】18847

【品名】(2S,3R)-3-(tert-butoxy)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]butyric acid

【CA登记号】

【分子式】C₂₃H₂₇NO₅

【分子量】397.47112

【元素组成】C 69.5% H 6.85% N 3.52% O 20.13%

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：(XVIII)

Successive deprotection/coupling cycles of peptide resin (XV) with Fmoc-L-Val-OH (XVI), Fmoc-L-Thr(tBu)-OH (XVIII), Fmoc-D-Val-OH (I) and 5-methylhexanoic acid (XXI) give peptide resins (XVII), (XIX), (XX) and (XXII), respectively.

参考文献中间体

合成目标

【1】 Royo, M.; Manzanares, I.; Lopez, A.; Jimenez, J.C.; Albericio, F.; Giralt, E.; Rodrigues, I. (PharmaMar, SA); Kahalalide cpds.. WO 0158934 .

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)	43354	(2R)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-methylbutyric acid		C₂₀H₂₁NO₄	详情	详情
(XV)	49385	(2-chlorophenyl)(diphenyl)methyl (9S,12R,15R,18R,21R)-15-[(1R)-1-[((2S)-2-[[(allyloxy)carbonyl]amino]-3-methylbutanoyl)oxy]ethyl]-9-[([1-[(2R)-2-amino-3-methylbutanoyl]-2-pyrrolidinyl]carbonyl)amino]-21-isopropyl-2,2-dimethyl-12,18-bis[(1S)-1-methylpropyl]-4,10,13,16,19-pentaoxo-3-oxa-5,11,14,17,20-pentaazadocosan-22-oate		C₆₉H₁₀₀ClN₉O₁₄	详情	详情
(XVI)	19932	(2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-methylbutyric acid		C₂₀H₂₁NO₄	详情	详情
(XVII)	49386	(2-chlorophenyl)(diphenyl)methyl (9S,12R,15R,18R,21R)-15-[(1R)-1-[((2S)-2-[[(allyloxy)carbonyl]amino]-3-methylbutanoyl)oxy]ethyl]-9-([[1-((2R)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-methylbutanoyl)-2-pyrrolidinyl]carbonyl]amino)-21-isopropyl-2,2-dimethyl-12,18-bis[(1S)-1-methylpropyl]-4,10,13,16,19-pentaoxo-3-oxa-5,11,14,17,20-pentaazadocosan-22-oate		C₇₄H₁₀₉ClN₁₀O₁₅	详情	详情
(XVIII)	18847	(2S,3R)-3-(tert-butoxy)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]butyric acid		C₂₃H₂₇NO₅	详情	详情
(XIX)	49387	(2-chlorophenyl)(diphenyl)methyl (9S,12R,15R,18R,21R)-15-[(1R)-1-[((2S)-2-[[(allyloxy)carbonyl]amino]-3-methylbutanoyl)oxy]ethyl]-9-[[(1-[(2R)-2-[((2S)-2-[[(2S)-2-amino-3-(tert-butoxy)butanoyl]amino]-3-methylbutanoyl)amino]-3-methylbutanoyl]-2-pyrrolidinyl)carbonyl]amino]-21-isopropyl-2,2-dimethyl-12,18-bis[(1S)-1-methylpropyl]-4,10,13,16,19-pentaoxo-3-oxa-5,11,14,17,20-pentaazadocosan-22-oate		C₈₂H₁₂₄ClN₁₁O₁₇	详情	详情
(XX)	49388			C₈₇H₁₃₃ClN₁₂O₁₈	详情	详情
(XXI)	27649	5-methylhexanoic acid	628-46-6	C₇H₁₄O₂	详情	详情
(XXII)	49389	(2-chlorophenyl)(diphenyl)methyl (9S,12R,15R,18R,21R)-15-[(1R)-1-[((2S)-2-[[(allyloxy)carbonyl]amino]-3-methylbutanoyl)oxy]ethyl]-9-[[(1-[(2R,5S,8S,11R)-8-[1-(tert-butoxy)ethyl]-2,5,11-triisopropyl-17-methyl-4,7,10,13-tetraoxo-3,6,9,12-tetraazaoctadec-1-anoyl]-2-pyrrolidinyl)carbonyl]amino]-21-isopropyl-2,2-dimethyl-12,18-bis[(1S)-1-methylpropyl]-4,10,13,16,19-pentaoxo-3-oxa-5,11,14,17,20-pentaazadocosan-22-oate		C₉₄H₁₄₅ClN₁₂O₁₉	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Compound (XI) was prepared by solid phase peptide synthesis on a Rink amide 4-methylbenzhydrylamine (MBHA) resin. After removal of Fmoc protecting group from the resin with 20% piperidine in N-methyl-2-pyrrolidinone (NMP), a coupling cycle was carried out with Fmoc-Thr(O-t-Bu)OH (I) using bromotripyrrolidino phosphonium hexafluorophosphate (PyBroP) and diisopropylethylamine (DIEA) in NMP, followed by Fmoc removal with 20% piperidine in NMP. To the Thr-bound resin (II) they were stepwise coupled in subsequent coupling and deprotecting cycles the following amino acids: Fmoc- (N-allyloxycarbonylpropyl)PheOH (IV), Fmoc-ValCl (VI), Fmoc-Lys(Boc)OH (VIII), and Fmoc-D-TrpOH (X) to yield the corresponding peptide-bound resins (V), (VII), (IX) and (XI), respectively.

参考文献中间体

合成目标

【1】 Gilon, C.; et al.; A backbone-cyclic, receptor 5-selective somatostatin analogue: Synthesis, bioactivity, and nuclear magnetic resonance conformational analysis. J Med Chem 1998, 41, 6, 919.
【2】 Hornik, V.; Seri-Levy, A.; Gellerman, G.; Gilon, C. (Yissum Research Development Co.); Conformationally constrained backbone cyclized somatostatin analogs. WO 9804583 .

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)	18847	(2S,3R)-3-(tert-butoxy)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]butyric acid		C₂₃H₂₇NO₅	详情	详情
(II)	18848	9H-fluoren-9-ylmethyl (1S,2R)-1-(aminocarbonyl)-2-(tert-butoxy)propylcarbamate		C₂₃H₂₈N₂O₄	详情	详情
(III)	18849	(2S,3R)-2-amino-3-(tert-butoxy)butanamide		C₈H₁₈N₂O₂	详情	详情
(IV)	18850	(2S)-2-[[4-(allyloxy)-4-oxobutyl][(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-phenylpropionic acid		C₃₁H₃₁NO₆	详情	详情
(V)	18851	allyl 4-[((1S)-2-[[(1S,2R)-1-(aminocarbonyl)-2-(tert-butoxy)propyl]amino]-1-benzyl-2-oxoethyl)amino]butanoate		C₂₄H₃₇N₃O₅	详情	详情
(VI)	18852	9H-fluoren-9-ylmethyl (1S)-1-(chlorocarbonyl)-2-methylpropylcarbamate	103321-53-5	C₂₀H₂₀ClNO₃	详情	详情
(VII)	18853	allyl 4-[((1S)-2-[[(1S,2R)-1-(aminocarbonyl)-2-(tert-butoxy)propyl]amino]-1-benzyl-2-oxoethyl)[(2S)-2-amino-3-methylbutanoyl]amino]butanoate		C₂₉H₄₆N₄O₆	详情	详情
(VIII)	18854	(2S)-6-[(tert-butoxycarbonyl)amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]hexanoic acid		C₂₆H₃₂N₂O₆	详情	详情
(IX)	18855	allyl (10S,13S)-10-amino-15-((1S)-2-[[(1S,2R)-1-(aminocarbonyl)-2-(tert-butoxy)propyl]amino]-1-benzyl-2-oxoethyl)-13-isopropyl-2,2-dimethyl-4,11,14-trioxo-3-oxa-5,12,15-triazanonadecan-19-oate		C₄₀H₆₆N₆O₉	详情	详情
(X)	18856	(2R)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-(1H-indol-3-yl)propionic acid		C₂₆H₂₂N₂O₄	详情	详情
(XI)	18857	allyl (10S,13S)-15-((1S)-2-[[(1S,2R)-1-(aminocarbonyl)-2-(tert-butoxy)propyl]amino]-1-benzyl-2-oxoethyl)-10-[[(2R)-2-amino-3-(1H-indol-3-yl)propanoyl]amino]-13-isopropyl-2,2-dimethyl-4,11,14-trioxo-3-oxa-5,12,15-triazanonadecan-19-oate		C₅₁H₇₆N₈O₁₀	详情	详情

Extended Information