AN
2006:21112 DISSABS Order Number: AAI3185209
TI
ROMP approaches for organic synthesis and efforts toward the synthesis of
cyclipostins
AU
Poon, Wing Cheong [Ph.D.]; Hanson, Paul R. [advisor]
CS
The University of Kansas (0099)
SO
Dissertation Abstracts International, (2004) Vol. 66, No. 8B, p. 4231.
Order No.: AAI3185209. 155 pages.
ISBN: 0-542-26785-3.
DT
Dissertation
FS
DAI
LA
English
ED
Entered STN: 20060428
Last Updated on STN: 20060428
AB
The work reported herein describes the applications of ring-opening
metathesis polymerization (ROMP) using well-defined ruthenium-based
catalysts for organic synthesis, and efforts toward the synthesis of
cyclipostins.
A strategy to synthesize oligomeric sulfonamides employed both
ring-closing metathesis (RCM) and ring-opening metathesis polymerization
(ROMP). Amino acid-derived cyclic sulfonamides containing either exocyclic
or γ-endocyclic stereogenic centers were generated via RCM. These
cyclic sulfonamides underwent stereoselective Diels-Alder reactions to
yield endo-norbornenyl sulfonamides as major diastereomers. Subsequent
ROMP rapidly produced sulfonamide-based oligomers, and these oligomers
exhibited different solubility in a variety of solvents. Based on the
solubility difference of these oligomers, a capture-ROMP-release strategy
for the chromatography-free purification of Mitsunobu reaction products is
described. Oxo-norbornenyl-tagged reagents are utilized for standard
solution phase Mitsunobu chemistry. Post-reaction, phase-switching was
accomplished via in situ ROMP followed by precipitation of the polymer
with methanol. Release of the product from the polymer afforded amines and
alkyl hydrazine derivatives with good yields and purities.
The C-H activation strategy mediated by Rh2(OAc)4 was utilized toward
the synthesis of cyclipostins. This novel class of natural product
possesses strong inhibitory action against hormone-sensitive lipase
(HSL) and has potential in the development of therapeutic agents to
regulate lipolysis for the treatment of noninsulin-dependent diabetes
mellitus (NIDDM). The initial results of this project are reported.
CC
0490 CHEMISTRY, ORGANIC; 0487 CHEMISTRY, BIOCHEMISTRY