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|Title: ||Studies toward the synthesis and structural elucidation of chamuvarinin|
|Authors: ||Vanga, Raghava Reddy|
|Supervisors: ||Florence, Gordon John|
|Issue Date: ||2009|
|Abstract: ||Chamuvarinin (22) is a unique annoanceaeous acetogenin isolated from the roots of
Senegalese medicinal plant Uvaria chamae by Laurens and co-workers in 2004. It
displays highly potent cytotoxicity towards the cervical cancer cell lines (KB 3-1, IC₅₀=
0.8 nM). Structurally, chamuvarinin is the first reported acetogenin to contain an
adjacently linked bis-THF-THP ring system spanning the C15-C28 carbon backbone.
However, initial efforts to assign the relative and absolute configuration within this
stereochemical array, on the basis of ¹H and ¹³C NMR analysis, provided only partial
information pertaining to the relative configuration of C15-C19 region. As a
consequence, 32 diastereomeric structural possibilities exist for the highly unusual
structure of chamuvarinin; an unrealistic target for total synthesis. The synthesis of the
central core tricyclic (BCD) intermediate represents the most challenging aspect in the
entire synthesis, which in turn will aid ultimate structural proof.
At the outset of the project the stereochemical configuration of C15-C28 (BCD) of
chamuvarinin was uncertain and a library approach was proposed to enable structure
elucidation (Scheme A-1). Chapter 2 and Chapter 3 detail the synthesis of possible
diastereomers of the C9-C21 (51) and C22-C34 fragments (52). Chapter 4 details the
intial strategy to couple the key diastereomeric fragments in a series of model studies.
Chapter 5 describes the successful coupling strategy via an revised synthetic approach to
reach the advanced C9-C34 intermediate 251 (Scheme A-2).|
|Publisher: ||University of St Andrews|
|Appears in Collections:||Chemistry Theses|
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