The chromane core and its corresponding derivatives are common pharmacophores found in biologically-active compounds across multiple therapeutic areas. For example, during the course of Merck’s medicinal chemistry program aimed at treating Type II diabetes, a series of biaryl chromanes, exemplified by 1, were identified as potent and selective GPR40 receptor agonists. Likewise, in the area of women’s health, cis-2,3-substituted isoflavanones 2, and dihydrobenzoxathiins 3, were discovered as selective estrogen receptor subtype modulators for the treatment of osteoporosis and breast cancer. In order to access the unique structural arrangement, stereochemical requirement, and substitution pattern present in these chromanes and corresponding derivatives, we have developed several novel stereoselective syntheses utilizing a combination of conventional and biocatalysis approaches. These efforts will be the subject of this presentation.

GPR40 agonists and selective estrogen receptor subtype modulators: the stereoselective syntheses of novel chromanes, isoflavanones, and dihydrobenzoxathiins

ACS Spring Meeting 2021

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