THESIS
2016
xv, 569 pages : illustrations ; 30 cm
Abstract
This PhD thesis was composed of five chapters: a short and highly flexible [3+2+1]
synthetic strategy for the synthesis of THP-containing (±)-diospongin A was developed in
chapter one, a concise total synthesis of spiroketal-containing aculeatin A in both racemic and
enantioselective fashions was described in chapter two, first asymmetric total syntheses of (−)-penicipyrone and (−)-tenuipyrone were accomplished through a biomimetic cascade
polycyclization process in chapter three, and synthetic model studies of alotaketal A and
ansellone A were completed by syntheses of tricyclic spiroketal core structure and 12,13-dihydroansellone A, respectively, through cascade process in chapter four. After these chapters,
a summary of the total work in chapter five and the appendix containing...[
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This PhD thesis was composed of five chapters: a short and highly flexible [3+2+1]
synthetic strategy for the synthesis of THP-containing (±)-diospongin A was developed in
chapter one, a concise total synthesis of spiroketal-containing aculeatin A in both racemic and
enantioselective fashions was described in chapter two, first asymmetric total syntheses of (−)-penicipyrone and (−)-tenuipyrone were accomplished through a biomimetic cascade
polycyclization process in chapter three, and synthetic model studies of alotaketal A and
ansellone A were completed by syntheses of tricyclic spiroketal core structure and 12,13-dihydroansellone A, respectively, through cascade process in chapter four. After these chapters,
a summary of the total work in chapter five and the appendix containing NMR spectra and X-ray
data were attached.
Chapter one discussed the syntheses of substituted tetrahydropyran-4-ones (THPOs) by
developing a short and highly flexible [3+2+1] synthetic strategy, with high diastereoselectivity,
featuring 1,3-dipolar cycloaddition of α,β-unsaturated nitrile oxides, SmI
2-promoted
chemoselective reductive ring opening of isoxazolines and Amberlyst 15 mediated 6-endo-trig
oxa-Michael cyclization. This synthetic strategy was successfully applied in the concise
diastereoselective total synthesis of (±)-diospongin A in 8 steps with 20% overall yield from
known compound.
Chapter two described a concise total synthesis of aculeatin A as a single spiroisomer
featuring (i) phenol oxidative dearomatization and double intramolecular oxa-Michael addition
to construct the single spiroisomeric 5,6-spiroketal framework of aculeatins and (ii) chemo-and/
or stereoselective reduction of ketone to install the required secondary alcohol at C4 as the
final step.
Chapter three gave the first and concise asymmetric total syntheses of (−)-penicipyrone
and (−)-tenuipyrone by developing a biomimetic cascade cyclization strategy, featuring
intermolecular Michael addition/cycloketalization (or spiroketalization) process. Later, we
studied the cascade Michael addition/cycloketalization (or spiroketalization) reaction of cyclic
1,3-dicarbonyl compounds and α,β-unsaturated carbonyl compounds and found that under
acidic conditions the tethered alcohol of the α,β-unsaturated carbonyl compounds plays a
critical role in the regioselectivity and reactivity. On the basis of these findings, a detailed
mechanism for the cascade Michael addition/cycloketalization (or spiroketalization) reaction
was proposed and 43 analogues of penicipyrone and tenuipyrone were prepared in good to
excellent yields via this cascade strategy.
Chapter four disclosed a new cascade synthetic strategy and successfully implemented in
our model studies of synthesis of tricyclic spiroketal core of alotaketal A and synthesis of 12,
13-dihydroansellone A. The new cascade reaction represented the first example of
intramolecular nucleophilic opening of vinyl epoxide with ketonic/acetal oxygen nucleophile.
During the course of study, a reliable route for preparation of optically active triene by Bamford-Stevens reaction was developed, and a sequenced allylic chlorination/S
N2(/S
N2′) substitution
was utilized to install the allylic hydroxyl group in the late stage. The strategy provided the
viability for a collective synthesis of natural products.
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