Pharmaceuticals that contain polycyclic hydrocarbon scaffolds

Abstract

Numerous variations on structural motifs exist within pharmaceutical compounds that have entered the clinic. These variations have amounted over many decades based on years of drug development associated with screening natural products and de novo synthetic systems. Caged (or bridged) bicyclic structural elements offer a variety of diverse features, encompassing three-dimensional shape, and assorted pharmacokinetic properties. This review highlights approximately 20 all carbon cage containing pharmaceuticals, ranging in structure from bicyclo[2.2.1] through to adamantane, including some in the top-selling pharmaceutical bracket. Although, a wide variety of human diseases, illnesses and conditions are treated with drugs containing the bicyclic motif, a common feature is that many of these lipophilic systems display CNS and/or neurological activity. In addition, to an extensive overview of the history and biology associated with each drug, a survey of synthetic methods used to construct these entities is presented. An analysis section compares natural products to synthetics in drug discovery, and entertains the classical caged hydrocarbon systems potentially missing from the clinic. Lastly, this unprecedented review is highly pertinent at a time when big pharma is desperately trying to escape flatland drugs.

Exhaled breath profiles in the monitoring of loss of control and clinical recovery in asthma

“…Bicyclic rings are considered as interesting moieties. Molecules with such components are known as bioactive, can serve as organic core for peptides and are used in drugs . Two of three GC/MS compounds and the composite principal component 1 were associated with sputum eosinophil percentage, which suggests that at least part of the breath signal during loss and restoration of asthma control was derived from a flare‐up and suppression of eosinophilic airways inflammation, respectively.…”

Acyclic Quaternary Carbon Stereocenters via Enantioselective Transition Metal Catalysis

“…1 The vast majority of chemical products that incorporate non-racemic quaternary carbon stereocenters derive from the chiral pool. 2, 3 This fact reflects unmet challenges posed by the de novo chemical synthesis of stereocenters bearing four different carbon substituents. 4–13 Orbital overlap is more difficult to achieve in the formation of such highly congested stereocenters, and, in the case of enantioselective processes, defining the approach of chiral reagents or catalysts is intrinsically more challenging.…”

Enantioselective synthesis of an ophiobolin sesterterpene via a programmed radical cascade

“…Terpenes represent a highly diverse class of natural products whose derivatives have been developed into numerous FDA-approved drugs for the treatment of cancer, bacterial infection, malaria, and various other human diseases (1,2). Despite these successes, terpenes can pose unique challenges to medicinal research owing to often-limited commercial availability, difficulties in making deep-seated structural modifications, and incompletely elucidated biosynthetic pathways.…”