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 antihypertensivedrug (S,R,R,R)-nebivolol. Noteworthy is
chromans have become attractive synthetic targets in academia and pharmaceutical industry [1]. Nebivolol (1, Figure 1) is a chroman-based antihypertensivedrug that was first reported in the racemic form [2][3]. Chiral HPLC was subsequently employed to access various stereoisomers of 1 in enantiomerically
first use of the Sharpless asymmetric dihydroxylation as the sole source of chirality for the synthesis of nebivolol intermediates.
The chroman-based antihypertensivedrug nebivolol, its biologically active stereoisomers and late-stage intermediates for its synthesis.
Synthetic strategies toward late
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Graphical Abstract
Figure 1:
The chroman-based antihypertensive drug nebivolol, its biologically active stereoisomers and late-s...
Beilstein J. Org. Chem.2010,6, No. 25, doi:10.3762/bjoc.6.25
. This methodology overcomes many of drawbacks associated with previously reported syntheses.
Keywords: antihypertensivedrug; oxazoline hydrolysis; Suzuki coupling; Telmisartan; Introduction
Telmisartan (1) is an angiotensin II receptor antagonist useful in the treatment of hypertension, heart
diseases, heart attack, and bladder diseases [1][2][3]. Telmisartan is currently available in the market as an antihypertensivedrug [4] under the brand name of Micardis®.
Essential hypertension is a major risk factor in cardiovascular diseases and is responsible for one-third of global deaths. Most
antihypertensivedrug Telmisartan has been developed, featuring a Suzuki cross-coupling for the construction of the biaryl moiety and a regiospecific reductive amination-condensation sequence for the synthesis of the central benzimidazole.
Experimental
All solvents and reagents were purchased from the commercial
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Graphical Abstract
Figure 1:
The angiotensin II receptor antagonist Telmisartan.