The aim of this project the development of a flexible and modular synthesis of the biologically active
furanocembranolide providencin, which would also provide access to suitable structural analogues for the
evaluation of their biological activities.
Providencin has been isolated from the seaplume Pseudopterogorgia kallos, which was collected in the
Southwestern Carribean Sea near Providencia Island. This macrocyclic natural product of the furanocembranolide
family was shown to exhibit in vitro anticancer activity against human breast (MCF7), lung (NCI-H460) and CNS
(SF-268) cancer cell lines.
The objective of this project is the efficient enantio- and diastereocontrolled synthesis of the furanocembranolide
providencin which is flexible enough to allow the preparation of suitable analogs to evaluate the pharmacophoric
region of the molcule. Due to its interesting profile of biologic activities, providencin could thus serve as a lead
structure for novel drugs against various kinds of cancer. Owing to the complex functionalization and interesting
molecular architecture of this target the total synthesis is a highly challenging and rewarding task which certainly
will lead to novel insights in synthetic methodology. Furthermore, the availability from natural sources is extremely
limited which gives a persuasive motivation for the total synthesis.
The structural similarity between providencin and another furanocembranolide, bielschowskysin suggests a strong
biogenetic relationship which could be uncovered by means of chemical synthesis. Thus, the total synthesis of
providencin would provide a platform for the synthesis of bielschewskysin via similar precursors.