合成路线1

Synthesis of the target Sanglifehrin A: The condensation of the chiral ketone (XXXVII) with aldehyde (XXXVIII) by means of Sn(OTf)2 and TEA in dichloromethane gives the beta-hydroxyketone (XXXIX), which is reduced with Me4NBH3CN to yield the diol (XL). The ketalization of (XL) by means of DDQ, followed by ration with Tes-Cl and imidazole affords the silylated ketal (XLI), which is cleaved with iBu2AlH and oxidized with (COCl)2 to provide the protected carbaldehyde (XLII). The stereocontrolled condensation of aldehyde (XLII) with the chiral acetylenic ketone intermediate (XXIV) by means of (+)-DIPCl and TEA in ethyl ether leads to the acetylenic ketone (XLIII). This is reduced with Me4NBH3CN and ketalized by means of 2,2-dimethoxypropane and PPTS (simultaneous desilylation takes place) to give the dihydroxy ozonide (XLIV). The protection of the primary OH group of (XLIV) by means of Piv-Cl, pyridine and DMAP yields the pivalate (XLV), which is silylated with Tes-Cl and imidazole and deprotected with iBu2AlH to afford the acetylenic alcohol (XLVI). The sequential oxidation of (XLVI) with DMP and with NaClO2, followed by methylation with diazomethane affords the methyl ester (XLVII), which is treated with Me2AlNH2 in dichloromethane to provide the corresponding amide (XLVIII). The desilylation of (XLVIII) by means of TBAF, followed by oxidation with DMP gives the delta-ketoester (XLIX), which is submitted to and acid ring closure with CSA to yield the spirolactam (L)