Part I. Studies of Stereoselective C-H Amination, Part II. Synthetic Studies of Edaxadiene, Part III. Studies towards the Synthesis of Alchivemycin A, Part IV. The Formal Synthesis of (-)-Englerin A by RRCM and Etherification
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Authors
Lee, Jungyong
Issue Date
1-Aug-12
Type
Dissertation
Language
en_US
Keywords
Alternative Title
Abstract
Part I.
Various polysaccharides and glycosidic antibiotics including
anthracycline and vancomycin have been widely used to treat cancer or
infection. Amino sugars are often found in their structures and play an
important role in biological activities. C-H amination is one of
valuable methods to streamline the synthesis of C-N bond. Regio-,
stereoselective C-H amination has been studied to produce useful amino
sugars from glycals and alkynol carbamates. Part II. Edaxadiene was
considered as a new diterpene that had biological activities to inhibit
the infection process of Mycobacterium tuberculosis. We describe a
design to access a bicyclic backbone, which is the core structure of
this compound by an intramolecular Diels-Alder (IMDA) reaction. Part
III. Progress toward the synthesis of a key moiety of alchivemycin A,
which was isolated from a plant-derived actinomycete Streptomyces sp and
displayed selective and potent antibiotic activity against Micrococcus
luteus, has been focused on the construction of a bicyclic structure by
the IMDA reaction. Part IV. (-)-Englerin A is a natural product from
phyllathus engleri, a plant common in east Africa. It showed an
interesting biological activity in its ability to inhibit the growth of
kidney cancer cell lines in the NCI-60 screen. The useful bioactivity
and unique structure of (-)-englerin A have inspired many scientists to
develop synthetic approaches to understand the structure-activity
relationship (SAR). We reported the formal synthesis of (-)-englerin A
and established an efficient synthetic route by a relay ring closing
metathesis (RRCM) reaction and etherification. This study includes the
efficient opening of the epoxide ring of a Β-substituted
Α-epoxy alcohol under the lithium acetylide reagent, the relay
ene-yne-ene metathesis method for the preparation of a diene that is
disubstituted on both ends, and the transannular stereo- and
regio-specific oxymercuration of the C-6, C-7 olefin in the guaiane ring
system.
Description
370 pg.
Citation
Publisher
The Graduate School, Stony Brook University: Stony
Brook, NY.