【结 构 式】 |
【分子编号】41838 【品名】3-[(4S)-3-(tert-butoxycarbonyl)-5-oxo-1,3-oxazolidin-4-yl]propionic acid 【CA登记号】 |
【 分 子 式 】C11H17NO6 【 分 子 量 】259.25912 【元素组成】C 50.96% H 6.61% N 5.4% O 37.03% |
合成路线1
该中间体在本合成路线中的序号:(II)The cyclization of N-Boc-L-glutamic acid (I) with paraformaldehyde in refluxing DCE gives the oxazolidinone (II), which is benzylated with benzyl bromide and LiHMDS in THF yielding the benzyl derivative (III). The reaction of (II) with CDI in THF affords the activated acid (IV), which is condensed with the protected glutamic acid (V) by means of LiHMDS in THF to provide the adduct (VI). The decarboxylation of the allyloxycarbonyl group of (VI) by means of a Pd catalyst furnishes the compound (VII), which is deprotected and cyclized by hydrogenation with H2 over Pd/C and PtO2 to give the substituted proline (VIII). The lactam cyclization of (VIII) by means of NaOH in methanol, followed by crystallization yields the bicyclic carboxylic acid (IX), which is condensed with the arginine derivative (X) by means of EDC, HOBT and DIEA in THF affording the adduct (XI). The oxidation of the OH group of (XI) with DMP in dichloromethane gives the precursor (XII), which is finally deprotected by a treatment with TFA and PhS-Me. The intermediate arginine derivative (X) has been obtained as follows: The condensation of the fully protected arginine aldehyde derivative (XIII) with benzothiazole (XIV) by means of n-BuLi in ethyl ether gives the adduct (XV), which is then treated with TFA in order to eliminate the Boc protecting groups and furnish the desired arginine derivative intermediate (X).
【1】 Lee, M.S.; Eguchi, M.; Gardner, B.S.; Boatman, P.D.; Kahn, M.; Kim, H.-O.; Nakanishi, H.; Synthesis of dipeptide secondary structure mimetics. Proc. 15th Am. Pep. Symposium, Kluwer Acad. Publ. 1998, 212. |
【2】 Nakanishi, H.; Ogbu, C.O.; Shea, J.P.; Cao, B.; Kahn, M.; Boatman, P.D.; Kim, H.-O.; Eguchi, M.; Secondary structure peptide mimetics: Design, synthesis, and evaluation of beta-strand mimetic thrombin inhibitors. J Med Chem 1999, 42, 8, 1367. |
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) | 12895 | (2S)-2-[(tert-Butoxycarbonyl)amino]pentanedioic acid | 2419-94-5 | C10H17NO6 | 详情 | 详情 |
(II) | 41838 | 3-[(4S)-3-(tert-butoxycarbonyl)-5-oxo-1,3-oxazolidin-4-yl]propionic acid | C11H17NO6 | 详情 | 详情 | |
(III) | 41839 | 3-[(4R)-4-benzyl-3-(tert-butoxycarbonyl)-5-oxo-1,3-oxazolidin-4-yl]propionic acid | C18H23NO6 | 详情 | 详情 | |
(IV) | 41840 | tert-butyl (4R)-4-benzyl-4-[3-(1H-imidazol-1-yl)-3-oxopropyl]-5-oxo-1,3-oxazolidine-3-carboxylate | C21H25N3O5 | 详情 | 详情 | |
(V) | 41841 | 5-allyl 1-benzyl (2S)-2-[[(benzyloxy)carbonyl]amino]pentanedioate | C23H25NO6 | 详情 | 详情 | |
(VI) | 41842 | 1-allyl 5-benzyl (4S)-2-[3-[(4R)-4-benzyl-3-(tert-butoxycarbonyl)-5-oxo-1,3-oxazolidin-4-yl]propanoyl]-4-[[(benzyloxy)carbonyl]amino]pentanedioate | C41H46N2O11 | 详情 | 详情 | |
(VII) | 41843 | tert-butyl (4R)-4-benzyl-4-((6S)-7-(benzyloxy)-6-[[(benzyloxy)carbonyl]amino]-3,7-dioxoheptyl)-5-oxo-1,3-oxazolidine-3-carboxylate | C37H42N2O9 | 详情 | 详情 | |
(VIII) | 41844 | (2S,5R)-5-[2-[(4R)-4-benzyl-3-(tert-butoxycarbonyl)-5-oxo-1,3-oxazolidin-4-yl]ethyl]-2-pyrrolidinecarboxylic acid | C22H30N2O6 | 详情 | 详情 | |
(IX) | 41485 | 4-chloro-1-methyl-2-nitrobenzene;4-chloro-2-nitrotoluene;4-chloro-1-methyl-2-nitro-benzene | 89-59-8 | C7H6ClNO2 | 详情 | 详情 |
(X) | 40421 | N-[(4S)-4-amino-5-(1,3-benzothiazol-2-yl)-5-hydroxypentyl]-N'-[(4-methoxyphenyl)(diphenyl)methyl]guanidine | C33H35N5O2S | 详情 | 详情 | |
(XI) | 41846 | tert-butyl (3S,6R,8aR)-3-[([(1S)-1-[1,3-benzothiazol-2-yl(hydroxy)methyl]-4-[(imino[[(4-methoxyphenyl)(diphenyl)methyl]amino]methyl)amino]butyl]amino)carbonyl]-6-benzyl-5-oxooctahydro-6-indolizinylcarbamate | C54H61N7O6S | 详情 | 详情 | |
(XII) | 41847 | tert-butyl (3S,6R,8aR)-3-[([(1S)-1-(1,3-benzothiazol-2-ylcarbonyl)-4-[(imino[[(4-methoxyphenyl)(diphenyl)methyl]amino]methyl)amino]butyl]amino)carbonyl]-6-benzyl-5-oxooctahydro-6-indolizinylcarbamate | C54H59N7O6S | 详情 | 详情 | |
(XIII) | 41848 | tert-butyl (Z)-([(4S)-4-[(tert-butoxycarbonyl)amino]-5-oxopentyl]amino)[[(4-methoxyphenyl)(diphenyl)methyl]amino]methylidenecarbamate | C36H46N4O6 | 详情 | 详情 | |
(XIV) | 36784 | 1,3-benzothiazole | 95-16-9 | C7H5NS | 详情 | 详情 |
(XV) | 41849 | tert-butyl (Z)-([(4S)-5-(1,3-benzothiazol-2-yl)-4-[(tert-butoxycarbonyl)amino]-5-hydroxypentyl]amino)[[(4-methoxyphenyl)(diphenyl)methyl]amino]methylidenecarbamate | C43H51N5O6S | 详情 | 详情 |