合成路线1

Sharpless epoxidation of (XIII) with cumene hydroperoxide, diisopropyl L-tartrate ((+)-DIPT) and Ti(O-i-Pr)4 affords epoxide (-)-(XIV), which is then treated with benzyl isocyanate and NaH in refluxing THF to yield oxazolidinone (XV). Oxidation of (XV) by means of CrO3 in H2SO4 (Jones reagent) in acetone gives the corresponding carboxylic acid (XVI), which is converted into methyl ester (XVII) via diazomethane esterification in Et2O. Exposure of (XVII) to ethanolic KOH affords the trans-acid (XVIII), which is then converted into (2R,3S)-hydroxyleucine (XIX) by treatment with KOH and hydrogenolysis over Pd(OH)2 in MeOH. Esterification of (XIX) by means of MeOH and HCl (gas) provides (XX), which is treated with methyl benzimidate (Ph(MeO)C=NH) or methyl orthobenzoate (PhC(OMe)3) in the presence of catalytic p-TsOH to yield trans-oxazoline (XXI). Aldol condensation of (XXI) with formaldehyde and LHMDS via the Seebach protocol gives (XXII), which is converted into (XXIII) via Moffat oxidation with DCC and TFA in benzene/DMSO. Brown asymmetric allylboration of (XIII) in THF with (E)-crotyl(diisopinocampheyl)borane (XXIV) in Et2O affords a homoallylic alcohol mixture from which diastereomer (-)-(XXV) is obtained. Ozonolysis of (-)-(XXV) and reductive treatment with dimethylsulfide (DMS), followed by oxidation with NaClO2, NaH2PO4 and 2-methyl-2-butene, provides carboxylic acid (XXVI), which is then converted into (X) by means of Pd and HCOONH4 in refluxing HOAc followed by saponification with NaOH. Lactam ester derivative (X) reacts with N-acetyl-L-cysteine allyl ester (XXVII), BOPCl and Et3N in CH2Cl2 to furnish (XVIII), which is finally deallylated by means of Pd(PPh3)4, HCO2H and Et3N in THF.