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【结 构 式】

【分子编号】61511

【品名】dibenzyl (2R,5R)-5-((2S)-3-(benzyloxy)-2-{[4-(benzyloxy)-3,5-dichlorobenzoyl]amino}-3-oxopropyl)-2-((1S,2S)-2-{[(benzyloxy)carbonyl]amino}-1,3-dihydroxypropyl)-1,2-pyrrolidinedicarboxylate

【CA登记号】

【 分 子 式 】C55H53Cl2N3O12

【 分 子 量 】1018.94424

【元素组成】C 64.83% H 5.24% Cl 6.96% N 4.12% O 18.84%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XIV)

The condensation of lactone (V) -prepared from L-proline by the Seebach method- with aldehyde (VI) -prepared from L-serine by the Garner method- by means of LDA in THF gives a mixture of the syn and anti alcohols (VII) and (VIII). The minor compound (VII) is converted into the desired enantiomer by oxidation with DMP, followed by reduction with NaBH4. The treatment of (VIII) with 10% H2SO4 causes an intramolecular transacetalization of the t-butyloxazoline and simultaneous hydrolysis of the dimethyloxazoline. The resulting product is benzylated at the carboxyl group and silylated with Tbdps-Cl to afford the bicyclic oxazolidine (IX). The hydrolysis of (IX) with acetic acid and subsequent protection of the resulting secondary alcohol with Tms-Cl provides the pyrrolidine (X), which is oxidized with MeReO3/urea/H2O2 to give the nitrone (XI). The condensation of (XI) with the iodopropionic intermediate (IV) by means of Zn and CuI in THF/water yields the hydroxylamine (XII), which is reduced with Zn and NH4Cl, and then protected with Cbz-Cl/K2CO3 to afford the carbamate (XIII). The removal of the silyl protecting groups of (XIII) by means of Tms-Cl in methanol provides the diol (XIV), which is selectively oxidized at the primary OH group by means of 4-methoxy-TEMPO and NaClO2 to give the carboxylic acid (XV). Finally, hydrogenolysis of the benzylic protecting groups of (XV) by means of H2 over Pd/C in ethanol/chloroform affords the target kaitocephalin

1 Watanabe, H.; Okue, M.; Kobayashi, H.; Kitahara, T.; The first synthesis of kaitocephalin based on the structure revision. Tetrahedron Lett 2002, 43, 5, 861.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(IV) 61502 benzyl (2R)-2-{[4-(benzyloxy)-3,5-dichlorobenzoyl]amino}-3-iodopropanoate C24H20Cl2INO4 详情 详情
(V) 33128 (3R,7aS)-3-(tert-butyl)tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazol-1-one C10H17NO2 详情 详情
(VI) 61503 benzyl (4S)-4-formyl-2,2-dimethyl-1,3-oxazolidine-3-carboxylate C14H17NO4 详情 详情
(VII) 61504 benzyl (4S)-4-[(R)-[(3R)-3-(tert-butyl)-1-oxodihydro-1H-pyrrolo[1,2-c][1,3]oxazol-7(5H)-yl](hydroxy)methyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate C24H34N2O6 详情 详情
(VIII) 61505 benzyl (4S)-4-[(S)-[(3R)-3-(tert-butyl)-1-oxodihydro-1H-pyrrolo[1,2-c][1,3]oxazol-7(5H)-yl](hydroxy)methyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate C24H34N2O6 详情 详情
(IX) 61506 benzyl (1R,3S)-1-((S)-{[(benzyloxy)carbonyl]amino}{[tert-butyl(diphenyl)silyl]oxy}methyl)-3-(tert-butyl)dihydro-1H-pyrrolo[1,2-c][1,3]oxazole-7a(5H)-carboxylate C43H52N2O6Si 详情 详情
(X) 61507 benzyl (2R)-2-{(1S,2S)-2-{[(benzyloxy)carbonyl]amino}-3-{[tert-butyl(diphenyl)silyl]oxy}-1-[(trimethylsilyl)oxy]propyl}-2-pyrrolidinecarboxylate C42H54N2O6Si2 详情 详情
(XI) 61508 (2R)-2-[(benzyloxy)carbonyl]-2-{(1S,2S)-2-{[(benzyloxy)carbonyl]amino}-3-{[tert-butyl(diphenyl)silyl]oxy}-1-[(trimethylsilyl)oxy]propyl}-3,4-dihydro-2H-pyrrolium-1-olate C42H52N2O7Si2 详情 详情
(XII) 61509 benzyl (2R,5R)-5-((2S)-3-(benzyloxy)-2-{[4-(benzyloxy)-3,5-dichlorobenzoyl]amino}-3-oxopropyl)-2-{(1S,2S)-2-{[(benzyloxy)carbonyl]amino}-3-{[tert-butyl(diphenyl)silyl]oxy}-1-[(trimethylsilyl)oxy]propyl}-1-hydroxy-2-pyrrolidinecarboxylate C66H73Cl2N3O11Si2 详情 详情
(XIII) 61510 dibenzyl (2R,5R)-5-((2S)-3-(benzyloxy)-2-{[4-(benzyloxy)-3,5-dichlorobenzoyl]amino}-3-oxopropyl)-2-{(1S,2S)-2-{[(benzyloxy)carbonyl]amino}-3-{[tert-butyl(diphenyl)silyl]oxy}-1-[(trimethylsilyl)oxy]propyl}-1,2-pyrrolidinedicarboxylate C74H79Cl2N3O12Si2 详情 详情
(XIV) 61511 dibenzyl (2R,5R)-5-((2S)-3-(benzyloxy)-2-{[4-(benzyloxy)-3,5-dichlorobenzoyl]amino}-3-oxopropyl)-2-((1S,2S)-2-{[(benzyloxy)carbonyl]amino}-1,3-dihydroxypropyl)-1,2-pyrrolidinedicarboxylate C55H53Cl2N3O12 详情 详情
(XV) 61512 (2R,3S)-3-{(2R,5R)-5-((2S)-3-(benzyloxy)-2-{[4-(benzyloxy)-3,5-dichlorobenzoyl]amino}-3-oxopropyl)-1,2-bis[(benzyloxy)carbonyl]pyrrolidinyl}-2-{[(benzyloxy)carbonyl]amino}-3-hydroxypropanoic acid C55H51Cl2N3O13 详情 详情
Extended Information