THESIS
2023
1 online resource (x, 167 pages) : illustrations (some color)
Abstract
Organic chemistry has been known for its use of many toxic and hazardous chemicals in organic
reactions, which are not sustainable and not applicable in a large-scale synthesis. The first
section of this thesis is to address this problem with Green Chemistry principles. Specifically,
the first chapter of this thesis is focused on development of a green protocol for synthetically
useful semi-pinacol rearrangement. Halogenative semi-pinacol rearrangement of allylic
alcohols has been widely used in organic synthesis. However, most existing halogenating
reagents including N-halosuccinimide (NCS, NBS and NIS), bromine, t-BuOCl, selectfluor,
and chloramine-T for halogenative semi-pinacol rearrangement are hazardous and toxic.
Our laboratory has a continuous interest in developing green protoc...[
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Organic chemistry has been known for its use of many toxic and hazardous chemicals in organic
reactions, which are not sustainable and not applicable in a large-scale synthesis. The first
section of this thesis is to address this problem with Green Chemistry principles. Specifically,
the first chapter of this thesis is focused on development of a green protocol for synthetically
useful semi-pinacol rearrangement. Halogenative semi-pinacol rearrangement of allylic
alcohols has been widely used in organic synthesis. However, most existing halogenating
reagents including N-halosuccinimide (NCS, NBS and NIS), bromine, t-BuOCl, selectfluor,
and chloramine-T for halogenative semi-pinacol rearrangement are hazardous and toxic.
Our laboratory has a continuous interest in developing green protocols for various
halogenation/oxidation reactions and we found that these two green protocols: Oxone/halide
and Fenton chemistry are applicable to halogenative semi-pinacol rearrangement. Chapter one
presents the development of Fenton chemistry for halogenative semi-pinacol rearrangement
with broad substrate scope, mechanistic studies, and subsequent transformations. The Fenton
chemistry for semi-pinacol rearrangement represents significant advancements in green
chemistry.
Chapter two of this thesis describes the diversity-oriented synthesis of analogues of marine
natural product lepadins. The Lepadin family has shown promising anticancer activities against
tumor cells. Our laboratory has achieved the collective total syntheses of seven members of
lepadins and found that they were a new class of ferroptosis induces. However, the anticancer
activity of lepadin natural products is moderate with ca. 5 μM IC
50 values. In order to improve
the anticancer potency and to establish the structure-activity relationship, we initiated the
diversity-oriented synthesis of lepadin analogues. Eleven lepadin analogues were synthesized,
characterized, and evaluated for their cytotoxicity using MTT. While no analogues were
identified with more potency than the natural lepadin E and H, we found that subtle structural
difference had considerable influence on the cytotoxicity, which might help elucidate the
structure-activity relationship in the future with more analogues are synthesized and evaluated.
The original copies of
1H and
13C NMR spectra are provided in the Appendix Section of this
thesis.
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