合成路线1

Hydrogenation of methyl butyrylacetate (I) in the presence of the chiral catalyst [RuCl2(BINAP)]2.Et3N furnished the (R)-hydroxyester (II). Alkylation of (II) with 3-bromo-2-methyl-1-propene (III) in the presence of lithium diisopropylamide gave the isobutenyl derivative (IV), which was further hydrogenated to (V) in the presence of Pd/C. After basic hydrolysis of the methyl ester of (V), the resulting carboxylic acid (VI) was coupled with 2-tetrahydropyranyloxyamine by means of EDC to provide the tetrahydropyranyl-protected hydroxamic acid (VII). Mesylation of the free hydroxyl group of (VII) to give (VIII), followed by its cyclization in the presence of potassium carbonate, gave rise to the azetidinone (IX). Opening of the lactam ring of (IX) with NaOH afforded the protected hydroxyamino acid (X). Then, formylation of the amino group with formic acetic anhydride in pyridine provided intermediate (XI).