Thesis-1989-Rogers-Evans.pdf (2.79 MB)
Synthetic approaches towards chiral leukotriene analogues
thesis
posted on 2012-11-26, 14:38 authored by Mark C. Rogers-EvansA review of the discovery, biological activity and chemical synthesis of
the leukotrienes is presented, together with the latest developments in their
structural modification to produce useful antagonists. Strategies are
presented for the preparation of chiral leukotriene derivatives in which
the characteristic triene unit is replaced by various aromatic groups and
include:
(i) The preparation and attempted separation of the racemic
diastereomers of methyl S-hydroxy-6-(2-methoxycarbonyl-
2-amino-ethylthio>-6-phenylhexanoate; (ii) A chemical synthesis involving the Sharpless asymmetricepoxidation
of (El-ethyl 4-hydroxy-6-phenylhex-S-enoate to (El-ethyl
S( R).6(S)-epoxy-6-phenyl-4(S)-hydroxyhexanoate followed by
selective de-oxygenation studies on the corresponding racemic
epoxy alcohol to give (E}-ethyIS.6-epoxy-6-phenyl-hexanoate; iii An enzymic route utilizing the porcine pancreatic lipase catalysed
hydrolysis of a number of racemic 3-alkyl-3-butanoyloxy-
1.2-epoxides to the corresponding chiral epoxy alcohols with various
degrees of selectivity. one of the most useful being the completely
enantioselective hydrolysis of the less polar diastereomer of·
(E)-3-butanoyloxy-I.2-epoxy-I-phenylhexane. The more
polar diastereomer was preferentially hydrolysed to
l( R),2(S)-epoxy-I-phenylhexan-3-( R)-ol, as verified by
Sharpless epoxidation of (E)-I-phenylhex-I-en-3-01.
History
School
- Science
Department
- Chemistry
Publisher
© M.C. Rogers-EvansPublication date
1989Notes
A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of Doctor of Philosophy of Loughborough University.Language
- en