Terpenoid diketone

The Hajos-Parrish reaction can be regarded as the enantioselective version of the Robinson annulation. In the early stages of the synthetic effort targeting the mixed polyketide-terpenoid metabolite (-)-austalide B, L.A. Paquette and co-workers used this transformation to prepare the key bicyclic precursor in enantiopure form. Ethyl vinyl ketone was reacted with 2-methyl-1,3-cyclopentanedione in the presence of catalytic amounts of L-valine to afford the bicyclic diketone with a 75% ee. 

Regio- and enantioselective reduction of diketones have been conducted successfully by biocafalysis. Examples for the reduction of diketones to hydroxyl ketones and diols are shown in Figure 11.11. Figure 11.11a shows the preparation of a key intermediafe for the synthesis of terpenoids by a baker s yeast-catalyzed reduction of a o-cyclohexanedione. DMSO (10%) was used to solubilize the substrate [67]. Figure 11.11b shows the reduction of 3,5-dioxo-6-(benzyloxy)hexanoic acid ethyl ester by Acinetobacter sp. SC 13874 to the corresponding si/n-(3R,5S)-diol, potential intermediates for die s)mthesis of HMG-CoA reducfase inhibitors, in 99.4% ee with 52-74% de depending on substrate concentrations (74% de in 2g/l and 52% de in lOg/1) [66]. After the reaction, XAD-16 resin was added to facilitate the recovery process by adsorbing the product. 

SCHEME 33.16. Reduction of diketones for the synthesis of (a) key intermediates for terpenoids and (b) HMG-Co A reductase inhibitors. 

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