Towards the total synthesis of the herqulines
Herqulines A and B (1 and 2 respectively) were isolated from the culture broth of a soilderived
Penicillium species in 1979 and 1996 respectively. They were both found to
inhibit platelet aggregation, with herquline B (whose stereochemistry has not been
elucidated) being the stronger inhibitor. The herqulines are thought to be
biosynthesised from tyrosine 3, but very little work relating to their total synthesis has
This thesis describes work towards the total synthesis of herqulines A and B, focussing
on two key reactions: the linking of two tyrosine molecules via the aromatic rings, and
the reduction of the aromatic rings to give the required pattern of unsaturation.
However, aryl-aryl bond formation followed by the symmetrical reduction of the
biphenyl system was not successful- the required regiochemistry of the reduction posed
a particular problem.
Although the target molecules 1 and 2 were not generated, strategies for their total
synthesis were investigated. The most recently examined approach, which avoided the
regiochemical problem mentioned above and involved the reduction of the aromatic
ring of tyrosine followed by the linking of two reduced tyrosine moieties, appears