The synthesis and biological evaluation of natural and unnatural cyclopentenone prostanoids
Research into the synthesis and biological properties of the cyclopentenone
prostaglandins has become the focus of many research groups over the past few years.
The ability for cyclopentenone prostaglandins, for example prostaglandin AI. to
reduce virus yields and inflammation, both in vitro and in vivo, and to act as anticancer
agents in vitro has made them important biological targets.
In view of this, a great deal of work is currently being undertaken towards the
preparation of cyclopentenone prostaglandin analogues, in the hope of harnessing the
innate biological activity of this system.
Part of the ongoing research into the cyclopentenone prostaglandins is the work
currently being undertaken at The University of Liverpool, and this Ph.D. thesis is
part of the contribution made by the Roberts' group.
This thesis begins with an introductory section, Chapter 1, outlining the background
and biological properties of the natural prostaglandins, along with examples of their
chemical syntheses and some of the work carried out on other, related
cyclopentenone-based natural products. Chapter 2 goes on to elaborate upon the biological results obtained during the course of this Ph.D., the synthesis of various
prostaglandin analogues and the discussion of these results. The latter part of Chapter
2 describes the synthesis and ultimately the revision of stereochemistry of a natural
product isolated from ascomycete strain A23-98.
It has been shown that a-iodo-cyclopentenone 160, generated in 7 steps from Dribose,
can undergo a palladium-catalysed Stille reaction, followed by deprotection of
the masked diol, to reveal the natural product syn-163.
steps i) (PhCNhPdCI2' CuI, AsPh]
HO""' ..~ -~
160 ii) PPTS, MeOH
Following the synthesis it was subsequently discovered that the geometry of the sidechain
is cis, as shown in syn-163, and not trans as proposed by NMR studies and
correlation to similar natural products.
Finally, Chapter 3 describes the experimental details associated with the compounds
prepared throughout this thesis, followed by a reference section giving relevant
citations in the chemical literature.