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【结 构 式】 
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【分子编号】53682 【品名】(2S)-2-({(2S)-2-[({(2S,4R)-1-[5-(9H-fluoren-9-ylmethoxy)-5-oxopentanoyl]-4-hydroxypyrrolidinyl}carbonyl)amino]propanoyl}amino)-3-hydroxypropanoic acid 【CA登记号】n/a |
【 分 子 式 】C30H35N3O9 【 分 子 量 】581.62272 【元素组成】C 61.95% H 6.07% N 7.22% O 24.76% |
合成路线1
该中间体在本合成路线中的序号：(XXVIII)Acylation of 9-fluorenylmethanol (XXV) with glutaric anhydride (XXVI) yielded the glutarate mono-ester (XV). This was further activated as the pentafluorophenyl ester (XXVII) upon treatment with pentafluorophenol and DCC. Coupling of active ester (XXVII) with tripeptide (XXIV) gave rise to the glutaryl tripeptide (XXVIII).
| 【1】 Kaufman, M.J.; Almarsson, O.; Nerurkar, M.J.; Lynch, J.E.; Karki, S.B.; Cameron, M.; Lieberman, D.R.; Robbins, M.A.; Shi, Y.-J. (Merck & Co., Inc.); Salt form of a conjugate useful in the treatment of prostate cancer. US 6355611; WO 0130804 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XV) | 53680 | 5-(9H-fluoren-9-ylmethoxy)-5-oxopentanoic acid | n/a | C19H18O4 | 详情 | 详情 |
| (XXIV) | 53678 | (2S)-3-hydroxy-2-{[(2S)-2-({[(2S,4R)-4-hydroxypyrrolidinyl]carbonyl}amino)propanoyl]amino}propanoic acid | n/a | C11H19N3O6 | 详情 | 详情 |
| (XXV) | 53679 | 9H-fluoren-9-ylmethanol | 24324-17-2 | C14H12O | 详情 | 详情 |
| (XXVI) | 15512 | Glutaric Anhydride; dihydro-2H-pyran-2,6(3H)-dione | 108-55-4 | C5H6O3 | 详情 | 详情 |
| (XXVII) | 53681 | 1-(9H-fluoren-9-ylmethyl) 5-(2,3,4,5,6-pentafluorophenyl) pentanedioate | n/a | C25H17F5O4 | 详情 | 详情 |
| (XXVIII) | 53682 | (2S)-2-({(2S)-2-[({(2S,4R)-1-[5-(9H-fluoren-9-ylmethoxy)-5-oxopentanoyl]-4-hydroxypyrrolidinyl}carbonyl)amino]propanoyl}amino)-3-hydroxypropanoic acid | n/a | C30H35N3O9 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXVIII)Coupling between N-Boc-L-serine (XXIX) and L-leucine benzyl ester (XXX) furnished the Boc-dipeptide (XXXI), which was deprotected by means of a solution of HCl in isopropyl acetate. The resultant seryl-leucine benzyl ester (XXXII) was condensed with N-Boc-L-glutamine (XXXIII) to afford (XXXIV), which after N-Boc deprotection yielded tripeptide ester (XXXV). Further coupling of (XXXV) with N-Boc-L-cyclohexylglycine (XXXVI), followed by acidic deprotection, gave tetrapeptide (XXXVII). This was finally acylated with the glutaryl tripeptide (XXVIII) to provide the desired peptide intermediate (XVII).
| 【1】 Kaufman, M.J.; Almarsson, O.; Nerurkar, M.J.; Lynch, J.E.; Karki, S.B.; Cameron, M.; Lieberman, D.R.; Robbins, M.A.; Shi, Y.-J. (Merck & Co., Inc.); Salt form of a conjugate useful in the treatment of prostate cancer. US 6355611; WO 0130804 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVII) | 53673 | (3S,6S,9S,12S,15S,18S)-12-(3-amino-3-oxopropyl)-9-cyclohexyl-1-{(2S,4R)-1-[5-(9H-fluoren-9-ylmethoxy)-5-oxopentanoyl]-4-hydroxypyrrolidinyl}-6,15-bis(hydroxymethyl)-18-isobutyl-3-methyl-1,4,7,10,13,16-hexaoxo-2,5,8,11,14,17-hexaazanonadecan-19-oic acid | n/a | C52H72N8O15 | 详情 | 详情 |
| (XXVIII) | 53682 | (2S)-2-({(2S)-2-[({(2S,4R)-1-[5-(9H-fluoren-9-ylmethoxy)-5-oxopentanoyl]-4-hydroxypyrrolidinyl}carbonyl)amino]propanoyl}amino)-3-hydroxypropanoic acid | n/a | C30H35N3O9 | 详情 | 详情 |
| (XXIX) | 20126 | (2S)-2-[(tert-butoxycarbonyl)amino]-3-hydroxypropionic acid | C8H15NO5 | 详情 | 详情 | |
| (XXX) | 22252 | Benzyl (2S)-2-amino-4-methylpentanoate; Benzyl (S)-leucinate | C13H19NO2 | 详情 | 详情 | |
| (XXXI) | 53672 | benzyl (2S)-2-({(2S)-2-[(tert-butoxycarbonyl)amino]-3-hydroxypropanoyl}amino)-4-methylpentanoate | n/a | C21H32N2O6 | 详情 | 详情 |
| (XXXII) | 53683 | benzyl (2S)-2-{[(2S)-2-amino-3-hydroxypropanoyl]amino}-4-methylpentanoate | n/a | C16H24N2O4 | 详情 | 详情 |
| (XXXIII) | 31820 | (2S)-5-amino-2-[(tert-butoxycarbonyl)amino]-5-oxopentanoic acid | 13726-85-7 | C10H18N2O5 | 详情 | 详情 |
| (XXXIV) | 53684 | benzyl (6S,9S,12S)-6-(3-amino-3-oxopropyl)-9-(hydroxymethyl)-12-isobutyl-2,2-dimethyl-4,7,10-trioxo-3-oxa-5,8,11-triazatridecan-13-oate | n/a | C26H40N4O8 | 详情 | 详情 |
| (XXXV) | 53685 | benzyl (2S)-2-[((2S)-2-{[(2S)-2,5-diamino-5-oxopentanoyl]amino}-3-hydroxypropanoyl)amino]-4-methylpentanoate | n/a | C21H32N4O6 | 详情 | 详情 |
| (XXXVI) | 35619 | (2S)-2-[(tert-butoxycarbonyl)amino]-2-cyclohexylethanoic acid | C13H23NO4 | 详情 | 详情 | |
| (XXXVII) | 53686 | benzyl (2S)-2-({(2S)-2-[((2S)-5-amino-2-{[(2S)-2-amino-2-cyclohexylethanoyl]amino}-5-oxopentanoyl)amino]-3-hydroxypropanoyl}amino)-4-methylpentanoate | n/a | C29H45N5O7 | 详情 | 详情 |