合成路线1

The intermediate propionic aldehyde (VI) has been obtained by two different ways: 1. The cyclization of 2-methoxy-4,6-dimethylpyridine-3-carboxylic acid methyl ester (I) with the cyclohexenone derivative (II) by means of LDA, followed by aromatization with DDQ gives the tricyclic ketone (III), which is methylated with Me-I and K2CO3 to yield the dimethoxyketone (IV). The desilylation of (IV) with TBAF affords the propanol derivative (V), which is finally submitted to a Swern oxidation to provide the desired intermediate, the propionic aldehyde (VI). 2. The reaction of pyridine-3-carboxylate (I) with LDA and CO2 gives the dicarboxylic hemiester (VII), which is hydrolyzed with KOH and anhydrized to yield the homophthalic anhydride (VIII). The cyclization of (VIII) with the alpha-sulfinylcyclohexenone (IX) by means of NaH affords the tricyclic ketone (X), which is methylated with Me-I and K2CO3 to provide the dimethoxyketone (XI). Finally, the ethyleneketal group of (XI) is hydrolyzed with TFA to furnish the desired intermediate, the propionic aldehyde (VI). The cyclization of (VI) by means of SmI2 gives the tetracyclic diol (XII), which is submitted to a Swern oxidation to yield the alpha-hydroxyketone (XIII). The dehydration of (XIII) by means of the Burgess reagent yields the cyclohexenone derivative (XIV), which is finally asymmetrically reduced to the (R)-alcohol (XV) by means of BH3 using a chiral borane as catalyst.