合成路线1

The condensation of lactone (V) -prepared from L-proline by the Seebach method- with aldehyde (VI) -prepared from L-serine by the Garner method- by means of LDA in THF gives a mixture of the syn and anti alcohols (VII) and (VIII). The minor compound (VII) is converted into the desired enantiomer by oxidation with DMP, followed by reduction with NaBH4. The treatment of (VIII) with 10% H2SO4 causes an intramolecular transacetalization of the t-butyloxazoline and simultaneous hydrolysis of the dimethyloxazoline. The resulting product is benzylated at the carboxyl group and silylated with Tbdps-Cl to afford the bicyclic oxazolidine (IX). The hydrolysis of (IX) with acetic acid and subsequent protection of the resulting secondary alcohol with Tms-Cl provides the pyrrolidine (X), which is oxidized with MeReO3/urea/H2O2 to give the nitrone (XI). The condensation of (XI) with the iodopropionic intermediate (IV) by means of Zn and CuI in THF/water yields the hydroxylamine (XII), which is reduced with Zn and NH4Cl, and then protected with Cbz-Cl/K2CO3 to afford the carbamate (XIII). The removal of the silyl protecting groups of (XIII) by means of Tms-Cl in methanol provides the diol (XIV), which is selectively oxidized at the primary OH group by means of 4-methoxy-TEMPO and NaClO2 to give the carboxylic acid (XV). Finally, hydrogenolysis of the benzylic protecting groups of (XV) by means of H2 over Pd/C in ethanol/chloroform affords the target kaitocephalin