Chiral -hydroxy

KHMDS = potassium hexamethyldisilazane s-BuOK = potassium 1-methylpropoxide LICA = lithium isopropylcyclohexylamide. b Refers to the RjS ratio at the newly generated a-hydroxy chiral carbon atom. 

The major rate-limiting enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl Coenzyme A reductase (HMG-CoA reductase), has been a therapeutic target for many research groups. A synthesis of the functionalized thiophene 172, prepared for its biological activity, illustrates the utility of 162 for the introduction of one of the hydroxy chiral centers present in the molecule. This chiral center is then exploited for the introduction of the second chiral hydroxy center. Treatment of aldehyde 169 with the double anion of 162 at —95 °C in THF affords as the major product 170 (98.8 1.2). Treatment of the adduct with excess tert-butylacetate enolate at — 78 °C followed by acidic work-up furnishes the jS-hydroxyketone 171 in 86% isolated yield. Chelation-controlled reduction of the ketone, accomplished by initial complexation of the ketone and the hydroxy group with triethylborane followed by sodium borohydride addition, provides the desired dihydroxyester 172 (Scheme 39) [47]. 

Cyclohexanecarboxaldehyde derivs., 2-hydroxy-, chiral 44, 561 Cyclohexanecarboxylic acids, 2-hydroxy-, 6-subst., chiral 43, 612... 

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See also in sourсe #XX -- [ ]

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