【药物名称】(S)-Bu-HIBO
化学结构式(Chemical Structure):
参考文献No.460732
标题:Excitatory amino acid receptor ligands: Resolution, absolute stereochemistry, and enantiopharmacology of 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid
作者:Johansen, T.N.; Ebert, B.; Brauner-Osborne, H.; Didriksen, M.; Christensen, I.T.; Soby, K.K.; Madsen, U.; Krogsgaard-Larsen, P.; Brehm, L.
来源:J Med Chem 1998,41(6),930-939
合成路线图解说明:

Cyclization of oxoester (I) with aqueous hydroxylamine at 0 C gave a mixture of two isoxazoles (II) and (III), which were separated by column chromatography. Methylation of (II) with ethereal diazomethane provided methyl ether (IV). This was regioselectively brominated with Br2 at 50 C to give bromomethyl compound (V). Further treatment with dimethyl acetamidomalonate (VI) and NaOMe in refluxing methanol gave (VII) (1). Then, hydrolysis and decarboxylation of malonate (VII) in refluxing 2 M HCl afforded racemic amino acid (VIII), and subsequent protection with di-tert-butyl dicarbonate gave carbamate (IX). Formation of the salt with (S)-1-phenylethylamine (X) and recrystallization from EtOH-Et2O provided pure (S)-amino acid as the phenylethylamine salt (XI). Free acid was obtained by treatment with acetic acid, and then a reflux in concentrated HBr effected hydrolysis of both methyl ether and carbamate groups to afford the target (S)-amino acid.

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