合成路线1

The oxidation of 4-(benzyloxy)-1-butanol (I) with oxalyl chloride gives the corresponding aldehyde (II), which is condensed with the phosphonate (III) by means of DBU and LiCl in acetonitrile to yield the 2-hexenoate (IV). The asymmetric aminohydroxylation of (IV) by means of tert-butyl carbamate, K2[OsO2(OH)4] and a chiral catalyst ((DHQD)2PHAL) in propanol/water affords the desired regioisomer (V). The introduction of an azido group into the alpha-position with retention of the configuration was accomplished by two Mitsunobu reactions. The reaction of (V) with benzoic acid, PPh3 and DEAD in THF gives the benzoyloxy compound (VI) with inverted stereochemistry, which is hydrolyzed with K2CO3 in methanol to yield the corresponding alcohol (VII). Then the reaction of (VII) with HN3, DEAD and PPh3 in THF affords the azide (VIII) with the right stereochemistry. The hydrolysis of the ester group of (VIII) by means of K2CO3 in methanol/water, followed by cleavage of the protecting carbamate group with TFA, provides the carboxylic acid (IX). The cyclization of (IX) by means of 2-chloro-1-methylpyridinium iodide (CMPI) and TEA in acetonitrile gives the azetidinone (X), which is reduced with PPh3 in THF/water to yield the aminoazetidinone (XI). The acylation of the amino group of (XI) with 2-phenoxyacetyl chloride (A) and NaHCO3 in aqueous acetonitrile affords the amide (XII). The hydrogenation of (XII) with H2 over Pd/C in ethanol affords the primary alcohol (XIII), which is finally oxidized with the Jones reagent to provide the target carboxylic acid intermediate (XIV).