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【结 构 式】 
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【分子编号】23487 【品名】(2R)-2-([[(2S)-1-((2S)-2-([(2S)-2-[(tert-butoxycarbonyl)amino]-4-methylpentanoyl]amino)-6-[[(ethylamino)(ethylimino)methyl]amino]hexanoyl)pyrrolidinyl]carbonyl]amino)propionic acid 【CA登记号】 |
【 分 子 式 】C30H55N7O7 【 分 子 量 】625.80968 【元素组成】C 57.58% H 8.86% N 15.67% O 17.9% |
合成路线1
该中间体在本合成路线中的序号：(IX)The synthesis of ganirelix was performed using usual solid-state peptide synthesis with a Beckman 990 or a 5.0 L Vega 296 automated solid-phase peptide synthesizer. The synthesis was initiated by condensation of chloromethylated polystyrene/divinylbenzene resin (Merrifieled resin) (II) with Boc-D-alanine (I) by means of cesium carbonate, giving Boc-D-ala-RESIN (III), which was submitted to successive cycles of deprotection with TFA or HCl and addition of a new protected amino acid by means of DCC or HOBt. The following amino acids were added successively: Boc-L-proline (IV), Nalpha-Boc-Nomega,N'omega-diethyl-L-homoarginine (VI), Boc-L-leucine (VIII), Nalpha-Boc-Nomega,N'omega-diethyl-D-homoarginine (X) and Boc-L-tyrosine (XII), yielding successively the peptide resins (V), (VII), (IX), (XI) and (XIII).
| 【1】 Robinson, J.3rd; Morgans, D.J.; Bingenheimer, W.; Arzeno, H.B.; Temporary serine protection in solid phase synthesis of LH-RH analogs. Int J Pept Protein Res 1993, 41, 4, 342. |
| 【2】 Castaner, J.; Leeson, P.; Rabasseda, X.; Ganirelix Acetate. Drugs Fut 1999, 24, 4, 393. |
| 【3】 Nestor, J.J. Jr.; McClure, N.L. (Syntex (USA), Inc.); Temporary minimal protection synthesis of LH-RH analogs. EP 0443532; JP 1992211096; US 5212288 . |
| 【4】 Nestor, J.J. Jr.; Vickery, B.H. (Syntex (USA), Inc.); Nonapeptide and decapeptide analogs of LHRH as LHRH antagonists. EP 0277829; JP 1988201199; US 4801577 . |
| 【5】 Vickery, B.H. (Syntex (USA), Inc.); LHRH antagonist analogs and 19-nor-progestational steroids for therapy. EP 0301850 . |
| 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) | 15859 | Boc-D-Alanine; (2R)-2-[(tert-butoxycarbonyl)amino]propionic acid | 7764-95-6 | C8H15NO4 | 详情 | 详情 |
| (IV) | 16734 | (2S)-1-(tert-butoxycarbonyl)tetrahydro-1H-pyrrole-2-carboxylic acid; N-alpha-t-BOC-L-proline; (2S)-1-(tert-butoxycarbonyl)-2-pyrrolidinecarboxylic acid | C10H17NO4 | 详情 | 详情 | |
| (V) | 23483 | (2R)-2-([[(2S)-1-(tert-butoxycarbonyl)pyrrolidinyl]carbonyl]amino)propionic acid | C13H22N2O5 | 详情 | 详情 | |
| (VI) | 23484 | (2S)-2-[(tert-butoxycarbonyl)amino]-6-[[(ethylamino)(ethylimino)methyl]amino]hexanoic acid | C16H32N4O4 | 详情 | 详情 | |
| (VII) | 23485 | (2R)-2-([[(2S)-1-((2S)-2-[(tert-butoxycarbonyl)amino]-6-[[(ethylamino)(ethylimino)methyl]amino]hexanoyl)pyrrolidinyl]carbonyl]amino)propionic acid | C24H44N6O6 | 详情 | 详情 | |
| (VIII) | 23663 | (2S)-2-[(tert-butoxycarbonyl)amino]-4-methylpentanoic acid；N-Boc-L-leucine | C11H21NO4 | 详情 | 详情 | |
| (IX) | 23487 | (2R)-2-([[(2S)-1-((2S)-2-([(2S)-2-[(tert-butoxycarbonyl)amino]-4-methylpentanoyl]amino)-6-[[(ethylamino)(ethylimino)methyl]amino]hexanoyl)pyrrolidinyl]carbonyl]amino)propionic acid | C30H55N7O7 | 详情 | 详情 | |
| (X) | 23488 | (2R)-2-[(tert-butoxycarbonyl)amino]-6-[[(ethylamino)(ethylimino)methyl]amino]hexanoic acid | C16H32N4O4 | 详情 | 详情 | |
| (XI) | 23489 | (2R)-2-[([(2S)-1-[(2S,5S,8R,14E)-8-[(tert-butoxycarbonyl)amino]-14-(ethylamino)-2-(4-[[(ethylamino)(ethylimino)methyl]amino]butyl)-5-isobutyl-4,7-dioxo-3,6,13,15-tetraaza-14-heptadecen-1-anoyl]pyrrolidinyl]carbonyl)amino]propionic acid | C41H77N11O8 | 详情 | 详情 | |
| (XII) | 23490 | (2S)-2-[(tert-butoxycarbonyl)amino]-3-(4-hydroxyphenyl)propionic acid | C14H19NO5 | 详情 | 详情 | |
| (XIII) | 23491 | (2R)-2-[([(2S)-1-[(2S,5S,8R,11S)-2,8-bis(4-[[(ethylamino)(ethylimino)methyl]amino]butyl)-11-(4-hydroxybenzyl)-5-isobutyl-15,15-dimethyl-4,7,10,13-tetraoxo-14-oxa-3,6,9,12-tetraazahexadec-1-anoyl]pyrrolidinyl]carbonyl)amino]propionic acid | C50H86N12O10 | 详情 | 详情 |