10.3987/com-95-7257
The research aimed to develop an efficient synthetic approach to the decalin unit, which is a key intermediate for the synthesis of compactin, a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and an effective hypocholesterolemic agent. The study focused on the microwave-accelerated intramolecular Diels-Alder reaction of substrates 5a-c, which were prepared from 3-ethoxy-2-cyclohexenone. The reaction involved the use of vinylmagnesium bromide, hydrochloric acid, lithium aluminum hydride, ethyl hydrogen malate, ethyl hydrogen fumarate, and BuLi with maleic anhydride. The researchers found that microwave irradiation significantly accelerated the reaction compared to conventional heating, leading to the formation of the desired exo adduct (7c) with high stereoselectivity. The resulting 7c was then converted to the decalin unit (2a) through a series of chemical reactions, thus accomplishing an effective synthesis of the decalin unit required for an approach to compactin.
10.1016/S0957-4166(00)86344-2
The research explores the asymmetric hydrolysis of meso diacetate using pig liver esterase to produce (1S,3R,5S)-(-)-4, which is a key intermediate for synthesizing the chiral lactone moiety in compactin. The study was prompted by a previous erroneous assignment of the absolute configuration of the hydrolyzed product. The researchers tested various enzymes and found that pig liver esterase (PLE) provided the best results, yielding (1S,3R,5S)-4 with 62% isolated yield, 91% conversion yield, and 87% enantiomeric excess. The absolute configuration of the product was confirmed using the exciton chirality method. The study also details the synthesis of the chiral lactone moiety from (-)-4 through a series of chemical transformations, including protection, oxidation, and lactonization steps. The research concludes with the successful synthesis of the lactone moiety of compactin, highlighting the effectiveness of PLE in asymmetric hydrolysis and providing a new synthetic route for chiral lactone compounds.
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