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【结 构 式】 
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【分子编号】31820 【品名】(2S)-5-amino-2-[(tert-butoxycarbonyl)amino]-5-oxopentanoic acid 【CA登记号】13726-85-7 |
【 分 子 式 】C10H18N2O5 【 分 子 量 】246.2634 【元素组成】C 48.77% H 7.37% N 11.38% O 32.48% |
合成路线1
该中间体在本合成路线中的序号：(XV)The deprotection-coupling procedure was repeated using N-Boc-L-leucine (XIII), and N-Boc-L-glutamine (XV), yielding the depsipeptide resins (XII) and (XIV), respectively. Further cleavage of the Boc group provided the deprotected depsipeptide resin (XVII).
| 【1】 Yanai, M.; Suguroi, T.; Solid-phase synthesis of cyclooctadepsipeptide N-4909 using a cyclization-cleavage method with oxime resin. J Antibiot 1999, 52, 9, 835. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XII) | 31823 | (6S,9S,12S,15R,18S,21S)-12-[2-(benzyloxy)-2-oxoethyl]-6,15-diisobutyl-9-isopropyl-2,2-dimethyl-18-[(1S)-1-methylpropyl]-21-(10-methylundecyl)-4,7,10,13,16,19-hexaoxo-3,20-dioxa-5,8,11,14,17-pentaazatricosan-23-oic acid | C54H91N5O12 | 详情 | 详情 | |
| (XIII) | 31818 | N-(tert-butoxycarbonyl)leucine | C11H21NO4 | 详情 | 详情 | |
| (XIV) | 31824 | (6S,9R,12S,15S,18R,21S,24S)-15-[2-(benzyloxy)-2-oxoethyl]-6,9,18-triisobutyl-12-isopropyl-2,2-dimethyl-21-[(1S)-1-methylpropyl]-24-(10-methylundecyl)-4,7,10,13,16,19,22-heptaoxo-3,23-dioxa-5,8,11,14,17,20-hexaazahexacosan-26-oic acid | C60H102N6O13 | 详情 | 详情 | |
| (XV) | 31820 | (2S)-5-amino-2-[(tert-butoxycarbonyl)amino]-5-oxopentanoic acid | 13726-85-7 | C10H18N2O5 | 详情 | 详情 |
| (XVI) | 31825 | (6S,9S,12R,15S,18S,21R,24S,27S)-6-(3-amino-3-oxopropyl)-18-[2-(benzyloxy)-2-oxoethyl]-9,12,21-triisobutyl-15-isopropyl-2,2-dimethyl-24-[(1S)-1-methylpropyl]-27-(10-methylundecyl)-4,7,10,13,16,19,22,25-octaoxo-3,26-dioxa-5,8,11,14,17,20,23-heptaazano | C65H110N8O15 | 详情 | 详情 | |
| (XVII) | 31826 | (3S,6S,9R,12S,15S,18R,21S,24S)-24,27-diamino-12-[2-(benzyloxy)-2-oxoethyl]-9,18,21-triisobutyl-15-isopropyl-6-[(1S)-1-methylpropyl]-3-(10-methylundecyl)-5,8,11,14,17,20,23,27-octaoxo-4-oxa-7,10,13,16,19,22-hexaazaheptacosan-1-oic acid | C60H102N8O13 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXXIII)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 |
合成路线3
该中间体在本合成路线中的序号：(XVII)Azepinone (X) was obtained by cyclization of Boc-L-lysine (IX) in the presence of NaHCO3 and BOP reagent. Subsequent alkylation of the lactam nitrogen of (X) with benzyl bromoacetate (XI) afforded (XII). After Boc deprotection of (XII) with trifluoroacetic acid, coupling with Boc-L-alanine (XIII) gave dipeptide (XIV). This was subjected to a further deprotection and coupling sequence with Boc-L-tryptophan (XV) to give tripeptide (XVI), and then with Boc-L-glutamine (XVII), yielding (XVIII). Acid deprotection of the Boc group of (XVIII), followed by coupling with p-hydroxyphenylpropionic acid (XIX) provided the peptide amide (XX).
| 【1】 Cristau, M.; et al.; Synthesis and biological evaluation of bombesin constrained analogues. J Med Chem 2000, 43, 12, 2356. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 42809 | (2S)-6-amino-2-[(tert-butoxycarbonyl)amino]hexanoic acid | C11H22N2O4 | 详情 | 详情 | |
| (X) | 42810 | L-(-)-N-alpha-Boc-amino-epsilon-caprolactam; tert-butyl (3S)-2-oxoazepanylcarbamate | 76944-95-1 | C11H20N2O3 | 详情 | 详情 |
| (XI) | 12869 | benzyl 2-bromoacetate | 5437-45-6 | C9H9BrO2 | 详情 | 详情 |
| (XII) | 42811 | benzyl 2-[(3S)-3-[(tert-butoxycarbonyl)amino]-2-oxoazepanyl]acetate | n/a | C20H28N2O5 | 详情 | 详情 |
| (XIII) | 26450 | Boc-L-Alanine;(S)-2-((tert-butoxycarbonyl)amino)propanoic acid;N-Boc-L-alanine; (2S)-2-[(tert-butoxycarbonyl)amino]propionic acid | 15761-38-3 | C8H15NO4 | 详情 | 详情 |
| (XIV) | 42812 | benzyl 2-[(3S)-3-([(2S)-2-[(tert-butoxycarbonyl)amino]propanoyl]amino)-2-oxoazepanyl]acetate | C23H33N3O6 | 详情 | 详情 | |
| (XV) | 16114 | N-alpha-t-BOC-L-tryptophan; (2S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-indol-3-yl)propionic acid | 13139-14-5 | C16H20N2O4 | 详情 | 详情 |
| (XVI) | 42813 | benzyl 2-[(3S)-3-[((2S)-2-[[(2S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-indol-3-yl)propanoyl]amino]propanoyl)amino]-2-oxoazepanyl]acetate | C34H43N5O7 | 详情 | 详情 | |
| (XVII) | 31820 | (2S)-5-amino-2-[(tert-butoxycarbonyl)amino]-5-oxopentanoic acid | 13726-85-7 | C10H18N2O5 | 详情 | 详情 |
| (XVIII) | 42814 | benzyl 2-((3S)-3-[[(2S,5S,8S)-8-(3-amino-3-oxopropyl)-5-(1H-indol-3-ylmethyl)-2,12,12-trimethyl-4,7,10-trioxo-11-oxa-3,6,9-triazatridec-1-anoyl]amino]-2-oxoazepanyl)acetate | C39H51N7O9 | 详情 | 详情 | |
| (XIX) | 25691 | 3-(4-hydroxyphenyl)propionic acid | 501-97-3 | C9H10O3 | 详情 | 详情 |
| (XX) | 42815 | benzyl 2-[(3S)-3-[((2S)-2-[[(2S)-2-[((2S)-5-amino-2-[[3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoyl)amino]-3-(1H-indol-3-yl)propanoyl]amino]propanoyl)amino]-2-oxoazepanyl]acetate | C43H51N7O9 | 详情 | 详情 |