Beilstein J. Org. Chem.2017,13, 571–578, doi:10.3762/bjoc.13.56
asymmetric synthesis of (R)-1-((R)-6-fluorochroman-2-yl)ethane-1,2-diol, (R)-1-((S)-6-fluorochroman-2-yl)ethane-1,2-diol and (S)-6-fluoro-2-((R)-oxiran-2-yl)chroman, which have been used as late-stage intermediates for the asymmetric synthesis of the antihypertensive drug (S,R,R,R)-nebivolol. Noteworthy is
that a large number of racemic and asymmetric syntheses of nebivolol and their intermediates have been described in the literature, however, the Sharpless asymmetric dihydroxylation has never been employed as the sole source of chirality for this purpose.
Keywords: dihydroxylation; epoxide-ring
opening; heterocycles; nebivolol; syn-epoxide; Findings
Chiral chromans are prevalent components of a large number of natural products, natural product-like molecules and pharmaceutical drugs, possessing diverse biological activities [1]. In view of their wide spectrum of biological profiles, chiral
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Graphical Abstract
Figure 1:
The chroman-based antihypertensive drug nebivolol, its biologically active stereoisomers and late-s...