合成路线1

Metalation of N-Boc-pyrrole (I) with the lithium amide of tetramethylpiperidine, followed by boronation with triethyl borate and acidic work-up leads to the pyrroleboronic acid (II). Subsequent catalytic hydrogenation over Pt/C provides the racemic pyrrolidineboronic acid (III). Alternatively, protection of pyrrolidine (IV) with Boc2O affords (V). After metalation of N-Boc-pyrrolidine (V) with s-butyllithium, treatment with triethyl borate gives rise to the boronic acid (III). Condensation of the racemic boronic acid (III) with (+)-pinanediol (VI) furnishes the corresponding mixture of diastereoisomeric pinanediol boronates, from which the desired isomer (VII) can be isolated by column chromatography. Further removal of the N-Boc protecting group under acidic conditions yields the pyrrolidineboronic ester (VIII). Coupling of pyrrolidine (VIII) with N-Boc-L-valine (IX) produces amide (X). The N-Boc group is then cleaved with HCl in Et2O to afford the deprotected amine (XI). Finally, removal of the pinanediol moiety by transesterification of the boronic ester (XI) with phenylboronic acid provides the desired boronic dipeptide