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The important requirement for approval of a new drug, in case it happens to be chiral, that both enantiomers of the drug be studied in detail [1], have focused the attention of synthetic organic and medicinal chemists on the development of new methods for catalytic asymmetric synthesis especially of relevant saturated N-heterocycles. Despite the success of chirally modified transition-metal catalysts in asymmetric synthesis, in the form of the Nobel Prize in Chemistry in 2001, the field of asymmetric organic synthesis has since then been dominated by organocatalysts due to their ability to catalyze a variety of fundamentally important transformations in medicinal chemistry and therefore chemical biology. One example is the Staudinger synthesis of β-lactams representing one class of saturated N-heterocycles and continuing to provide unique opportunities for the discovery of new derivatives with novel pharmacological profiles [2,3]. Specifically, β-lactams have recently been found to have potential as the basis for treatments for neurological disorders including amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease [4]. Although significant progress has been made in asymmetric organocatalytic Staudinger synthesis of β-lactams since the inaugural and pioneering investigations by Lectka and coworkers around the turn of the century [5,6], the same did not hold true regarding the development of a novel Gilman-Speeter process for the catalytic enantioselective synthesis of β-lactams [7]. Efforts directed at this latter goal are ongoing in this Laboratory.
Since piperazine derivatives have been reported to elicit a broad spectrum of pharmacological activities including antidepressant, anticancer, anti-helminthic, anti-bacterial, antifungal, anti-mycobacterial, anti-malarial, anti-tuberculant, anti-convulsant [8] and anti-AIDS [17]; one can easily comprehend that the sky will be the limit, as far as novel drug development is concerned, once this catalytic enantioselective process will be fully developed [18].
Finally, aziridines are structurally fascinating, pharmaceutically important, and finding applications in synthetic organic and medicinal chemistry [19-20]. Thus, they can be readily converted into a variety of nitrogen-containing compounds due to the inherent reactivity of the constrained three-membered ring present in biologically active natural products such as the azinomycins [21] and the mitomycins [22]. Novel catalytic enantioselective synthesis of aziridines as well as their employment in piperazine syntheses is under active investigation in this Laboratory [23-25].
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