| Summary: | 博士 === 國立清華大學 === 化學系 === 86 === The objective of this thesis is to find a rapid and efficient
synthetic methodfor taxane and its biogenetic precursor -- seco-
taxane. In the first section, we described the initial
approach for the taxane synthesis. The ring expansion of
bicyclo[3.3.0]octane to cyclooctane-ring and subsequently to
taxane B,C ring and taxane A,B ring. However this approach was
unsucessful. Later, we efficiently and successfully synthesized
taxane A-ring precursor, compound 219, with 53% yield. Then
compound 219 was subjected to Claisen rearrangement, reduction
and Swern oxidation to form compound 243, a taxane A-ring
analogue, with 42% overall yield. In the second section,
we described the utilization of compound 243 as starting
material in synthesis of taxane. Compound 243 on further
alkylation, phenylselenyl cyclization, deprotection and Swern
oxidation (4 steps) to yield a rigid compound 274 -- a taxane
precursor. The alkylation of compound 243 resulted in two
diastereomers 268 and 269. Compound 269 hence formed can be
converted to 268 by Mitsunobu esterification and hydrolysis.
Attempted intramolecular McMurry reductive cyclization on
compound 274 failed. Although the molecular model suggests that
the two carbonyls can be close enough to undergo cyclization,
NOE experiments on compound 274 at various temperature revealed
that the two carbonyl groups of compound 274 could be in close
proximity only at temperature above 60℃ which is much higher
than the McMurry coupling temperature. In the third
section, we described the use of compound 219 as starting
material in the synthesis of taxane and seco-taxane. The
compound 219 was converted to 302 and 303 by a series of
transformations including three key reactions: (1)
macrolactonization (2) Tebbe reaction and (3) Claisen
rearrangement. We tried to lactonize 278, 287 and 283
respectively to form 10-, 12-, and 14-member ring compounds,
However only 283 underwent lactonization and afforded the
14-member ring compound 282 in 75% yield. Compound 282 was
finally converted to compounds 302 and 303 in three steps, both
having bicyclo[9.3.0]pentadecane backbone.
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