Abstract:
Natural products are the molecules of nature; that is, they are molecules produced
by living organisms. These molecules are synthesised by living organisms using the
natural biosynthetic pathways. The total synthesis of such molecules using organic
reactions has been a challenge since the 1900s.
Calofolic Acids A-F are a class of natural products extracted from the bark of
Calophyllum scriblitifolium. These compounds are shown to have vasorelaxation
activity on phenylephrine-precontracted rat aortic rings. Through experiments, the
possible mechanism of activity of calofolic acid A was proposed. Calofolic acid A
inhibits the PI3K – AKT – PDE pathway in the VSMCs. This leads to the activation of
the cAMP – PKA – MYPT1 – MLC pathway as well as the cAMP – PKA – MYPT1 –
HSP 20 pathway. The overall effect of this is the vasorelaxation in the smooth
muscle cells in the rat aorta.
Herein, the efforts towards the total synthesis of the vasorelaxant natural product
calofolic acid – A are described. Two different routes with different strategies are
explored. The first route involved the synthesis of the chromanone core via alkene
reduction which had some problems associated with it. However, the second route
using a previously described work was successful and the total synthesis is nearing
its conclusion.
