【结 构 式】 |
【分子编号】41528 【品名】1-benzyl 4-(4-methoxybenzyl) (2S)-2-hydroxybutanedioate 【CA登记号】 |
【 分 子 式 】C19H20O6 【 分 子 量 】344.3642 【元素组成】C 66.27% H 5.85% O 27.88% |
合成路线1
该中间体在本合成路线中的序号:(III)The selective monobenzylation of the hydroxysuccinic acid (I) with trifluoroacetic anhydride and benzyl alcohol gives the monoester (II), which is esterified again with 4-methoxybenzyl chloride (PMB-Cl) and K2CO3 in hot DMF yielding the asymetric diester (III). The reaction of (III) with trifluoromethanesulfonic anhydride, CH3SNa and 15-crown-5 affords the methylsulfanyl derivative (IV), which is selectively debenzylated to give the hemiester (V). The condensation of (V) with the intermediate aminomethyl amide (VI) by means of EDAC and HOBT yields the expected amide (VII), which is oxidized with MCPBA or Oxone to afford the methylsulfanyl derivative (VIIIa-b). Unfortunately, during the preceding oxidation, during a variety of conditions, inevitably lead to epimerization of the stereocenter bearing the methylsulfonyl group. Finally (VIIIa-b) is deprotected by hydrogenolysis with Pd/C and formic acid in methanol. The intermediate aminomethyl amide (VI) has been obtained by condensation of N-benzyloxycarbonyl-L-alanine (X) with glycinamide (IX) by means of CDI and TEA in THF to give the dipeptide (XI), which is submitted to an acidic Hofmann rearrangement using I,I-bis(trifluoroacetoxy)iodobenzene (PIFA) yielding the desired aminomethyl amide (VI).
【1】 Sutton, A.E.; Clardy, J.; The total synthesis of pantocin B. Org Lett 2000, 2, 3, 319. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(VIIIa) | 41533 | benzyl (5S,12S)-5-methyl-12-(methylsulfonyl)-3,6,10-trioxo-1-phenyl-2-oxa-4,7,9-triazatridecan-13-oate | C24H29N3O8S | 详情 | 详情 | |
(VIIIb) | 41534 | benzyl (5S,12R)-5-methyl-12-(methylsulfonyl)-3,6,10-trioxo-1-phenyl-2-oxa-4,7,9-triazatridecan-13-oate | C24H29N3O8S | 详情 | 详情 | |
(I) | 11058 | (S)-(+)-Hydroxysuccinic acid; (S)-(+)-Malic acid; (S)-(+)-2-Hydroxybutanedioic acid; L-(-)-Apple acid | 97-67-6 | C4H6O5 | 详情 | 详情 |
(II) | 41527 | (3S)-4-(benzyloxy)-3-hydroxy-4-oxobutyric acid | C11H12O5 | 详情 | 详情 | |
(III) | 41528 | 1-benzyl 4-(4-methoxybenzyl) (2S)-2-hydroxybutanedioate | C19H20O6 | 详情 | 详情 | |
(IV) | 41529 | 1-benzyl 4-(4-methoxybenzyl) (2R)-2-(methylsulfanyl)butanedioate | C20H22O5S | 详情 | 详情 | |
(V) | 41530 | (3R)-4-(benzyloxy)-3-(methylsulfanyl)-4-oxobutyric acid | C12H14O4S | 详情 | 详情 | |
(VI) | 41531 | benzyl (1S)-2-[(aminomethyl)amino]-1-methyl-2-oxoethylcarbamate | C12H17N3O3 | 详情 | 详情 | |
(VII) | 41532 | benzyl (5S,12R)-5-methyl-12-(methylsulfanyl)-3,6,10-trioxo-1-phenyl-2-oxa-4,7,9-triazatridecan-13-oate | C24H29N3O6S | 详情 | 详情 | |
(IX) | 61209 | CBZ-L-Alanine; (2S)-2-[[(Benzyloxy)carbonyl]amino]propionic acid; N-((Phenylmethoxy)carbonyl)-alanine; Carbobenzyloxy-L-alanine | C11H13NO4 | 详情 | 详情 | |
(X) | 41435 | N'-[3-(tert-butyl)-5-methoxy-2-(methoxymethoxy)phenyl]-N-(3-pyridinyl)-N-(4-pyridinylmethyl)urea | C25H30N4O4 | 详情 | 详情 | |
(XI) | 41356 | tert-butyl (4R)-4-[[(benzyloxy)carbonyl]amino]-4-cyanobutanoate | C17H22N2O4 | 详情 | 详情 |