Beilstein J. Org. Chem.2023,19, 91–99, doi:10.3762/bjoc.19.9
mg/dL are considered hypercholesterimic. They are under high risk of cholelithiasis (formation of gallstones), atherosclerosis, heart attack, stroke, peripheral artery disease, and cancer [4][5]. Synergistic cholesterol lowering medications are inhibitors of cholesterol absorption (ezetimibe) and
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Graphical Abstract
Figure 1:
Chemical structure of three isomeric cholesterols.
Beilstein J. Org. Chem.2016,12, 1608–1615, doi:10.3762/bjoc.12.157
-reduction of an α,β-unsaturated ester to give a Reformatsky-type reagent, which in turn, reacted with an imine to give the syn-β-lactam. Additionally, the reaction was applied to the synthesis of (±)-ezetimibe, a potent β-lactamic cholesterol absorption inhibitor.
Keywords: β-lactam; ezetimibe; reductive
. Finally the method is applied for the new synthesis of ezetimibe, a potent β-lactamic cholesterol absorption inhibitor.
Results and Discussion
First of all, we tried to solve the drawbacks of the previously reported method and found that changing the catalyst to [RhCl(cod)]2 greatly improved the reaction
α,β-unsaturated lactone 2h, the β-lactam anti-3Ah that has a hydroxy group on the side chain was obtained in a low yield (Table 1, entry 11). This result was of interest because the reaction is applicable to the synthesis of ezetimibe. Ezetimibe is an inhibitor of the cholesterol transporter Niemann
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Graphical Abstract
Scheme 1:
The synthesis of syn-β-lactams using a reductive Mannich-type reaction.