合成路线1

C17-C27 Fragment: The monotosylation of 2,2-dimethylpropane-1,3-diol (XXIX) with TsCl and pyridine in CH2Cl2 gives the monotosylate (XXX), which is condensed with thiophenol by means of NaH in hot DMF yielding the phenylsulfanyl derivative (XXXI). The oxidation of (XXXI) with MCPBA in dichloromethane affords the corresponding sulfone (XXXII), which is oxidized with oxalyl chloride in DMSO to give the aldehyde (XXXIII). The Grignard reaction of (XXXIII) with 4-pentenylmagnesium bromide (XXXIV) in ethyl ether/CH2Cl2 yields the secondary alcohol (XXXV), which is oxidized with oxalyl chloride in DMSO to the ketone (XXXVI). The dihydroxylation of the double bond of (XXXVI) with K2OsO4 in t-BuOH/H2O followed by oxidation with NaIO4 in t-BuOH/H2O/THF affords the keto aldehyde (XXXVII), which is condensed with the chiral butanone (XXXVIII) by means of (-)-diisopinocampheyl chloride ((-)-DIP-Cl) and Et3N in dichloromethane to give aldol (XXXIX). The SmI2 catalyzed Tishchenko reduction of (XXXIX) in the presence of 4-nitrobenzaldehyde yields the diastereomerically pure 4-nitrobenzoate (XL), which is silylated with TBDMS-OTf to afford the protected ketone (XLI). The hydrolysis of the 4-nitrobenzoate group of (XLI) with LiOH in THF/MeOH/H2O gives the alcohol (XLII), which is cyclized by means of camphorsulfonic acid (CSA) in refluxing benzene yielding the dihydropyran (XLIII), the desired C17-C27 fragment. The intermediate, the chiral butanone (XXXVIII) has been obtained as follows: The optical resolution of 3-methyl-4-phenyl-3-buten-2-ol (XLIV) with (+)-DIPT gives the (R)-isomer (XLV), which is protected with p-methoxybenzyl bromide and NaH yielding the benzyl ether (XLVI). Finally, (XLVI) is ozonolyzed with O3 in MeOH / CH2Cl2 dichloromethane to afford the desired intermediate (XXXVIII).