A convergent synthesis of epothilone B that generates all seven of its
asymmetric centers in a completely stereoselective fashion has been
completed. Key reactions include an anti-Felkin aldol condensation to
set the C6 and C7 stereochemistry, a directed α-hydroxylation to install
the C15 (S)-hydroxyl substituent, and a Wittig condensation to...
Studies towards the total synthesis of (−)-kendomycin (1), a bacterial metabolite with
a unique molecular architecture and pronounced biological activity, are described. These
studies resulted in the synthesis of advanced intermediate 208, containing all of the
carbon atoms of 1.
A Dötz annulation between alkyne 122 and novel chromium carbenoid...
Avermectin Bia is a member of a class of medicinally important
natural products known for its potent antiparasitic activity and
interesting structural features. In this thesis, synthesis of a
model for the spiroketal portion of the avermectins is presented.
Oxidation of (S)-2-methylbutanol, followed by a stereoselective
chromium mediated reaction with...
Studies toward synthesis of subunits of sanglifehrin A, an immunosuppressant featuring a highly substituted [5,5]-spirolactam moiety as well as a 22-membered macrocycle are described. The macrolactone contains a peptidic backbone characterized by an unusual [beta]-substituted (S)-piperazic acid and (S)-m-hydroxyphenylalanine units. These studies resulted in the synthesis of advanced intermediate 358...
The ethyl acetate extract of the culture filtrate of the marine Ascomycete,
Leptosphaeria oraemaris (Linder) yielded a novel metabolite
designated by the common name leptosphaerin. An x-ray crystallographic
structure analysis was disproved by the synthesis of 3-acetoxy-S-(1,2-dihydroxyethyl)-
3-pyrrolin-2-one 1, starting with N,N-dibenzylhydroxylamine
47 and D-mannitol 44. Oxidation of 47 followed...
This thesis describes the development of a new enantioselective synthetic method employing chiral cis-2,5-diaminobicyclo[2.2.2]octane-based organometallic catalysts. The significance of this new method to organic synthesis is illustrated with preparation of enantioenriched products that are transformed to important pharmaceutical agents. Chapter 1 provides a brief historical overview of asymmetric catalysis, especially...
Rapamycin (5) was isolated in 1975 from the soil bacteria Streptomyces hygroscopicus and its structure was determined from spectroscopic techniques and an x-ray crystallographic analysis. Although it was initially found to exhibit antibiotic activity, it was subsequently shown to possess potent immunosuppressive activity as well.
Three approaches to the synthesis...
The first asymmetric synthesis of (-)-7-epicylindrospermopsin via intramolecular nitrone cycloaddition is described. The synthesis utilized a convergent approach to prepare the cycloaddition precursor 176, which was assembled by condensation of hydroxylamine 175 with aldehyde 145. Hydroxylamine 175 was synthesized from ethylene glycol (166) in seven steps. Aldehyde 145 was completed...