【结 构 式】 |
【分子编号】10907 【品名】methyl (2R,6S)-6-amino-2-[[(benzyloxy)carbonyl]amino]-7-([(1R)-1-methyl-2-[(4-nitrobenzyl)oxy]-2-oxoethyl]amino)-7-oxoheptanoate 【CA登记号】 |
【 分 子 式 】C26H32N4O9 【 分 子 量 】544.56164 【元素组成】C 57.35% H 5.92% N 10.29% O 26.44% |
合成路线1
该中间体在本合成路线中的序号:(XVII)2) The methylation of meso-2,6-bis(benzyloxycarbonylamino)heptanedioic acid (I) with diazomethane gives the corresponding dimethyl ester (XIII), which is submitted to a selective hydrolysis with a protease type VIII enzyme yielding the monoester (XIV). The cyclization of (XIV) with PCl5 affords the oxazolidinedione (XV), which is condensed with D-alanine 4-nitrobenzyl ester (XVI) to give compound (XVII) with a free amino group that is condensed with D-glutamic acid monoester (XI) affording the fully protected FK-565 derivative (XVIII), which is first debenzylated by hydrogenolysis to methyl ester (XIX), and finally hydrolyzed with NaOH.
【1】 Kolodziejczyk, A.M.; Stoev, S.; Kolodziejczyk, A.S.; New convenient synthesis of immunostimulating peptides containing meso-diaminopimelic acid. Syntheses of FK-565 and FK-156. Int J Peptide Protein Res 1992, 39, 282-7. |
【2】 Hoshi, A.; Castaner, J.; FK-565. Drugs Fut 1994, 19, 3, 243. |
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) | 10130 | (2R,6S)-2,6-Bis[[(benzyloxy)carbonyl]amino]heptanedioic acid | C23H26N2O8 | 详情 | 详情 | |
(XI) | 10901 | (4R)-5-(Benzyloxy)-4-(heptanoylamino)-5-oxopentanoic acid | C19H27NO5 | 详情 | 详情 | |
(XIII) | 10131 | dimethyl (2R,6S)-2,6-bis[[(benzyloxy)carbonyl]amino]heptanedioate | C25H30N2O8 | 详情 | 详情 | |
(XIV) | 10132 | (2S,6R)-2,6-Bis[[(benzyloxy)carbonyl]amino]-7-methoxy-7-oxoheptanoic acid | C24H28N2O8 | 详情 | 详情 | |
(XV) | 10133 | methyl (2R)-2-[[(benzyloxy)carbonyl]amino]-5-[(4S)-2,5-dioxo-1,3-oxazolan-4-yl]pentanoate | C17H20N2O7 | 详情 | 详情 | |
(XVI) | 10906 | 4-nitrobenzyl (2R)-2-aminopropanoate | C10H12N2O4 | 详情 | 详情 | |
(XVII) | 10907 | methyl (2R,6S)-6-amino-2-[[(benzyloxy)carbonyl]amino]-7-([(1R)-1-methyl-2-[(4-nitrobenzyl)oxy]-2-oxoethyl]amino)-7-oxoheptanoate | C26H32N4O9 | 详情 | 详情 | |
(XVIII) | 10908 | 14-benzyl 5-methyl (5R,9S,14R)-9-[([(1R)-1-methyl-2-[(4-nitrobenzyl)oxy]-2-oxoethyl]amino)carbonyl]-3,11,16-trioxo-1-phenyl-2-oxa-4,10,15-triazadocosane-5,14-dicarboxylate | C45H57N5O13 | 详情 | 详情 | |
(XIX) | 10909 | (2R)-5-[[(1S,5R)-5-Amino-1-([[(1R)-1-carboxyethyl]amino]carbonyl)-6-methoxy-6-oxohexyl]amino]-2-(heptanoylamino)-5-oxopentanoic acid | C23H40N4O9 | 详情 | 详情 |