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...
Verrucarol is the sesquiterpene portion of a number of macrocyclic di- and triesters of potential medicinal importance. In this study, a novel approach to the synthesis of this fungal metabolite is presented. An A-B-C route was investigated in which C-3 and C-4 of the C-ring were emplaced using a [2+2]...
The stereocontrolled synthesis of the southern lactone 17 of
boromycin and of the northern segments of both boromycin and aplasmomycin
are described. The syntheses begin with enantioselective
epoxidation of 3-buten-2-ol (42) to provide the optically active
2(S),3(R) epoxy alcohol 43. The absolute configuration was confirmed
by preparing 43 from (-)-2,3-dihydroxybutyric...
Alkylation of propylene oxide with 2-lithiofuran gave alcohol I,
which was smoothly converted to acetylfuran II. hydrogenation of II
over rhodium on charcoal followed by Jones' oxidation afforded ketone
III. Further transformation into IV was accomplished via a Wittig
reaction followed by saponification with methanolic sodium hydroxide.
Hydroboration of the...
Studies toward the total synthesis of (+)-providencin (1), a highly oxygenated cembranoid dipterpene with a unique bicyclo[12.2.0]hexadecane skeleton and pronounced biological activity, are described. These studies resulted in the synthesis of advanced intermediates 320 and 332 which contain all of the carbon atoms of 1. In a first generation approach...
Several approaches to the synthesis of penicillin from 2-iminothioazolidine
50, from 2-thiothiazolidine 66 and by photocyclization of
77 and 78 were investigated. 2-Iminothiazolidine 50 was prepared
from dibromoester 45 by the action of benzylamine followed by treatment
of aziridine 46 with potassium or ammonium thiocyanate. Attempted
introduction of a two-carbon...
An asymmetric approach to the synthesis of byssochlamic acid (1) is
described. Regioisomeric enzymatic differentiation is described in the selective
hydrolysis of dimethyl ester 30 by porcine liver esterase. Chiral dimethyl ester 42
was prepared by desymmetrization of cyclopentene 34 using porcine liver
esterase. A key intramolecular [2+2]cycloaddition-cycloreversion
photometathesis of...
PART I. The preparation of (-)-ibogamine (1) in fourteen steps from benzoquinone and in 10% overall yield is a powerful illustration of the value of the asymmetric Diels-Alder reaction as a starting point in a multistep synthesis. All four cycloadducts, 70, 77, 84 and 96, obtained with the (S)-BINOL-TiCl₂ complex...
Part I. The total synthesis of (+)-leptosphaerin (2), a metabolite of the marine
Ascomycete Leptosphaeria Oraemaris (Linder) was achieved, unambiguously
establishing both the relative and absolute stereochemistry of this natural product. This
synthesis also resolved the long-standing question of which of the isomeric structures 1
or 2 correctly represents the...