<div>Opposed to synthetic molecules, structures of natural products are not limited to human imagination and display a truly huge amount of variation. Principal component analysis of the chemical space occupied by natural products and synthetic molecules reveals much larger variance. More variance translates into more opportunities to find molecules that can interact with targets and be developed into drugs. More often than not, synthetically designed molecules too closely follow lapinskis rules of 5 and criteria for medicinal chemistry drug leads are far too stringent. Lapinski’s rule of 5, intended to be a rough guideline for designing drugs with compatible pharmacodynamic and pharmacokinetic properties is often taken too seriously, and the designing of drugs is severely inhibited as a result. This hinders the discovery of biologically useful chemicals, and is where nature steps in to break those boundaries. Natural products ‘natrually’ have a high hit ratio when being subject to screens (compared with synthetic molecules) and it is alarming how many of these naturally bioactive compounds have, what we consider, undesirable characteristics. This in itself can be used to broaden our knowledge of endogenous metabolism and we can apply our knowledge of undesirable functional groups to these natural products. 
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