BAL-1198, RO-0791198, -Drug Synthesis Database

【结构式】

【药物名称】BAL-1198, RO-0791198

【化学名称】Cyclo[D-alanyl-L-tyrosyl-L-valyl-4(R)-hydroxy-L-prolyl-D-allothreonyl-L-threonyl-3(S)-hydroxy-L-prolyl-3(R)-hydroxy-L-glutaminyl-glycyl-D-allothreonyl-Ndelta-(2-aminoethyl)-Ndelta-[N2,N2-bis(2-aminoethyl)-L-ornithyl]-L-ornithyl-3(R)-hydroxyhexadecanoyl-D-allothreonyl] pentakis(trifluoroacetate)

【CA登记号】351435-89-7 (stereoisomer, free base), 351495-78-8 (stereoisomer, free base)

【分子式】C₉₂H₁₄₆F₁₅N₁₉O₃₄

【分子量】2347.27232

【开发单位】Basilea Pharmaceutica (Proprietary), Roche (Originator)

【药理作用】Antifungal Agents, ANTIINFECTIVE THERAPY, 1,3-beta-Glucan Synthase Inhibitors

合成路线1 合成路线2 合成路线3

合成路线1

The requisite N-Boc protected tetraamino carboxylic acid (III) was prepared by reductive dialkylation of N-delta-Boc-L-ornithine (I) with N-Boc-aminoacetaldehyde (II) in the presence of sodium cyanoborohydride.

参考文献中间体

【1】 Masubuchi, K.; et al.; Synthesis and antifungal activities of novel 1,3-beta-D-glucan synthase inhibitor. Part 2. Bioorg Med Chem Lett 2001, 11, 10, 1273.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	58758	(2S)-2-amino-5-[(tert-butoxycarbonyl)amino]pentanoic acid	C₁₀H₂₀N₂O₄	详情	详情
(II)	58759	tert-butyl 2-oxoethylcarbamate	C₇H₁₃NO₃	详情	详情
(III)	58760	(2S)-2-(bis{2-[(tert-butoxycarbonyl)amino]ethyl}amino)-5-[(tert-butoxycarbonyl)amino]pentanoic acid	C₂₄H₄₆N₄O₈	详情	详情

合成路线2

The natural macrocyclic depsipeptide RO-0093655 (IV) was subjected to reductive alkylation with N-Boc-aminoacetaldehyde (II), yielding the mono-protected diamino compound (V). Subsequent acylation of amine (V) with the ornithine derivative (III) provided the corresponding amide (VI).

参考文献中间体

【1】 Masubuchi, K.; et al.; Synthesis and antifungal activities of novel 1,3-beta-D-glucan synthase inhibitor. Part 2. Bioorg Med Chem Lett 2001, 11, 10, 1273.
【2】 Okada, T.; et al.; Synthesis and antifungal activities of novel 1,3-beta-D-glucan synthase inhibitors. 223rd ACS Natl Meet (April 7 2002, Orlando) 2002, Abst MEDI 174.
【3】 Shimma, N.; Kobayashi, K.; Horii, I.; Yanagawa, A. (Basilea Pharmaceutica AG); Nasally administrable cyclic peptide compsns.. WO 0152894 .
【4】 Okada, T.; Shimma, N.; Murata, T.; Masubuchi, K.; Kohchi, M. (Basilea Pharmaceutica AG); Novel cyclic cpds.. EP 1254161; WO 0153322 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(II)	58759	tert-butyl 2-oxoethylcarbamate	C₇H₁₃NO₃	详情	详情
(III)	58760	(2S)-2-(bis{2-[(tert-butoxycarbonyl)amino]ethyl}amino)-5-[(tert-butoxycarbonyl)amino]pentanoic acid	C₂₄H₄₆N₄O₈	详情	详情
(IV)	50193	(3R)-3-[(2R,6S,9S,12R,15R,19R,22S,25R,31S,33aS,34S,39S,42R,44aS)-22-(3-aminopropyl)-2,34-dihydroxy-9-(4-hydroxybenzyl)-15,25,39,42-tetrakis[(1R)-1-hydroxyethyl]-6-isopropyl-12-methyl-5,8,11,14,17,21,24,27,30,33,38,41,44-tridecaoxo-19-tridecylnonatriacontahydro-1H,5H,21H-dipyrrolo[2,1-o:2,1-x][1,4,7,10,13,16,19,22,25,28,31,34,37]oxadodecaazacyclotetracontin-31-yl]-3-hydroxypropanamide	C₇₁H₁₁₆N₁₄O₂₃	详情	详情
(V)	58761	tert-butyl 2-[(3-{(2R,6S,9S,12R,15R,19R,22S,25R,31S,33aS,34S,39S,42R,44aS)-31-[(1R)-3-amino-1-hydroxy-3-oxopropyl]-2,34-dihydroxy-9-(4-hydroxybenzyl)-15,25,39,42-tetrakis[(1R)-1-hydroxyethyl]-6-isopropyl-12-methyl-5,8,11,14,17,21,24,27,30,33,38,41,44-tridecaoxo-19-tridecylnonatriacontahydro-1H,5H,21H-dipyrrolo[2,1-o:2,1-x][1,4,7,10,13,16,19,22,25,28,31,34,37]oxadodecaazacyclotetracontin-22-yl}propyl)amino]ethylcarbamate	C₇₈H₁₂₉N₁₅O₂₅	详情	详情
(VI)	58762		C₁₀₂H₁₇₃N₁₉O₃₂	详情	详情

合成路线3

The title compound was obtained by acidic cleavage of the Boc protecting groups of (VI) in the presence of trifluoroacetic acid.

参考文献中间体

【1】 Okada, T.; et al.; Synthesis and antifungal activities of novel 1,3-beta-D-glucan synthase inhibitors. 223rd ACS Natl Meet (April 7 2002, Orlando) 2002, Abst MEDI 174.
【2】 Masubuchi, K.; et al.; Synthesis and antifungal activities of novel 1,3-beta-D-glucan synthase inhibitor. Part 2. Bioorg Med Chem Lett 2001, 11, 10, 1273.
【3】 Okada, T.; Shimma, N.; Murata, T.; Masubuchi, K.; Kohchi, M. (Basilea Pharmaceutica AG); Novel cyclic cpds.. EP 1254161; WO 0153322 .
【4】 Shimma, N.; Kobayashi, K.; Horii, I.; Yanagawa, A. (Basilea Pharmaceutica AG); Nasally administrable cyclic peptide compsns.. WO 0152894 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	58762			C₁₀₂H₁₇₃N₁₉O₃₂	详情	详情

Extended Information