合成路线1

A new concise synthesis of nelfinavir has been reported: The asymmetric desymmetrization of the meso-epoxide (I) by means of azidotrimethylsilane and a chiral (R,R)-(salen)chromium(III) complex as catalyst gives the chiral 3-(trimethylsilyloxy)-4-azidotetrahydrofuran (II), which is deprotected with TFA in methanol yielding the chiral 4-azidotetrahydrofuran-3-ol (III). Hydrogenation of (III) with H2 over PtO2 affords the chiral 4-aminotetrahydrofuran-3-ol (IV), which is condensed with 3-acetoxy-2-methylbenzoyl chloride (V) by means of NaHCO3 in dichloromethane to provide amide (VI). The mesylation of the OH group of (VI) with Ms-Cl gives mesylate (VII), which is isomerized with Ac2O and H2SO4 to yield oxazoline (VIII). Condensation of compound (VIII) with the perhydroisoquinoline-3-carboxamide derivative (IX) by means of K2CO3 in methanol affords the oxazoline-adduct (X). Finally, the oxazoline-ring opening of compound (X) is performed with thiophenol (XI) and KHCO3.