合成路线1

Ether (III) was prepared by condensation of (S)-4-(hydroxymethyl)butyrolactone (I) and 4-fluorophenol (II) in the presence of diisopropylazodicarboxylate (DIAD) and triphenylphosphine under Mitsunobu conditions. Then, reduction of lactone (III) with DIBAL-H in toluene at -78 C gave lactol (IV), which was converted to silyl ether (V) by treatment with tert-butyldimethylsilyl chloride (TBDMS-Cl) and imidazole. Subsequent reaction of (V) with TBDMS-Br in CH2Cl2 at -78 C, followed by condensation with the lithium acetylide derived from acetylene (VI), yielded compound (VII) as a mixture of isomers. Chromatographic separation of the mixture provided the desired trans isomer, which was deprotected by treatment with tetra-n-butylammonium fluoride to give alcohol (VIII). This was then condensed with N,O-bis(phenoxycarbonyl)hydroxylamine (IX) in the presence of DIAD and Ph3P to furnish the hydroxamic acid derivative (X). Finally, concomitant deprotection of the O-phenoxycarbonyl group and substitution of the remaining phenoxy group for an amino group by treatment with methanolic ammonia in a pressure tube, provided the title compound.