1. Studies directed toward the total synthesis of aphidicolin. 2. A ring-metathesis cascade approach to novel rigid scaffolds derived from beta-amino acids.

Format:

Book

Thesis/Dissertation

Author/Creator:

Shepard, Stacey.

Contributor:

University of Pennsylvania.

Language:

English

Subjects (All):

Chemistry, Organic.

0490.

Local Subjects:

0490.

Physical Description:

630 pages

Contained In:

Dissertation Abstracts International 64-06B.

System Details:

Mode of access: World Wide Web.

text file

Summary:

This dissertation describes two independent research projects. The first section describes studies directed toward the total synthesis of aphidicolin, highlighting intramolecular dioxenone [2+2] photocycloaddition. This work demonstrates the utility of this methodology in the placement of an extraordinarily hindered C-9 quaternary stereocenter in the natural product, and broadens the scope of useful transformations for the introduction of the dioxenone chromophore into photosubstrates.

During construction of a 1,6-heptadiene precursor for straight photocycloaddition, a new method for the intact installation of the dioxenone chromophore into photosubstrates via conjugate addition of beta-ketoesters to a vinyl dioxenone was developed.

A second-generation strategy proposed a crossed photocycloaddition of a 1,5-hexadiene. To access this photosubstrate, the vinylogous Wolff rearrangement (VWR) was investigated. An alpha-diazo-beta-ketoester VWR precursor was also examined which resulted in dramatically improved yields of rearranged products. The resulting gamma,delta-unsaturated ester was elaborated into a diisopropyliminooxazinone-containing photosubstrate, irradiation of which afforded the unexpected product arising from the straight mode of photocycloaddition.

Transient B-ring opening alleviated steric hindrance at the C-9 ketone in the construction of a dioxenone-containing precursor to crossed photocycloaddition. Olefin and dioxenone moieties were installed at the open stage. Intramolecular Heck and radical cyclizations were explored for B-ring closure at the delta-position of the unsaturated dioxenone moiety. Radical cyclization furnished the dioxenone-containing photosubstrate, irradiation of which similarly afforded the straight photoadduct, contrary to the "rule of fives."

The second section describes the construction of novel rigid tricyclic scaffolds which have potential application as peptidomimetics. A ring-opening-closing cascade olefin metathesis of oxabicyclo[2.21]heptene-containing beta-amino acids afforded stereochemically complex scaffolds possessing two olefins which could be functionalized with groups important for recognition by a receptor of interest. Preliminary investigations of the metathesis of a beta-peptide dimer to a pentacyclic scaffold, including application of a salicylaldehyde-tethered strategy to circumvent the difficulty of medium-ring lactam formation, are also described.

Notes:

Source: Dissertation Abstracts International, Volume: 64-06, Section: B, page: 2680.

Supervisor: Jeffrey David Winkler.

Thesis (Ph.D.)--University of Pennsylvania, 2003.

Local Notes:

School code: 0175.

ISBN:

9780496435661

Access Restriction:

Restricted for use by site license.