Aldehydes
Aldrich ChemFiles 2007, 7.8, 3.
Aldrich ChemFiles 2007, 7.8, 3.
Hartmann and co-workers have described the synthesis of a series of potent and selective inhibitors of aldosterone synthase (CYP11B2), in which the key synthetic step was a Wittig reaction using various heterocyclic aldehydes (Scheme 1). The isoquinoline adduct was a very potent and selective inhibitor of CYP11B2. The successful inhibition of CYP11B2 has been proposed as a strategy for treatment of congestive heart failure and myocardial fibrosis.1
4-(1-Pyrrolidino)benzaldehyde was recently reported as a key building block in the synthesis of an improved inhibitor of NS5B polymerase of the hepatitis C virus (Scheme 2).2 The product from this substrate displayed significant improvement in the potency of the original HTS lead compound (Figure 1).
Scheme 2(678821)
Figure 1
Professor Jørgensen’s group has recently reported an asymmetric formal synthesis of (–)-paroxetine, a selective serotonin reuptake inhibitor used in the treatment of anxiety and other psychological disorders.3 The key step involved the organocatalytic conjugate addition of dibenzyl malonate to trans-4-fluorocinnamaldehyde (Scheme 3). Similarly, Wang’s research group has used the Jørgensen organocatalyst in a tandem Michael-aldol reaction to furnish chiral thiochromenes in excellent yields (Scheme 4).4
Scheme 3(683027)
Scheme 4(683027)
