The total synthesis of (+)-irciniastatin A.

Format:

Book

Thesis/Dissertation

Author/Creator:

Jurica, Jon A.

Contributor:

Winkler, Jeffrey D., advisor.

Smith, Amos B., III, advisor.

University of Pennsylvania.

Language:

English

Subjects (All):

Chemistry, Organic.

0490.

Penn dissertations--Chemistry.

Chemistry--Penn dissertations.

Local Subjects:

Penn dissertations--Chemistry.

Chemistry--Penn dissertations.

0490.

Physical Description:

381 pages

Contained In:

Dissertation Abstracts International 70-01B.

System Details:

Mode of access: World Wide Web.

text file

Summary:

The dissertation contained herein presents a first- and second-generation approach to (+)-irciniastatin A. Chapter One details the isolation and structural elucidation of (+)-irciniastatin A carried out independently by the laboratories of Professors Pettit and Crews. The chapter also describes all known biological data for (+)-irciniastatin A and (--)-irciniastatin B, a closely related congener. There have been two reported total syntheses of (+)-irciniastatin A, both of which will be discussed in detail.

The first-generation total synthesis of (+)-irciniastatin A is presented in Chapter Two. The cornerstone of our synthetic plan was construction of the tetrahydropyran core via an approach relying solely on catalyst control to generate each of the requisite stereocenters, permitting the synthesis of several analogues without major changes to the synthetic route. Initial synthesis of the tetrahydropyran core will permit late stage incorporation of the dihydroisocoumarin fragment via a boron enolate aldol. A one-pot Curtius rearrangement and subsequent amide bond union will provide the complete carbon skeleton for irciniastatin A. Initial studies revealed several problems with our choice of protecting groups. The use of several model systems resulted in a new protecting group strategy and identified a viable amide coupling strategy, which allowed completion of the full carbon skeleton and subsequent deprotection to provide (+)-irciniastatin A with a longest linear sequence of 30 steps in 2.2% overall yield.

The second-generation total synthesis of (+)-irciniastatin A is presented in Chapter Three. The second-generation approach focused on shortening the linear sequence of steps required to construct the tetrahydropyran fragment. Through a significant revision of the route, the longest linear sequence of steps to (+)-irciniastatin A was shortened to 21 steps in 5.2% overall yield.

Notes:

Thesis (Ph.D. in Chemistry) -- University of Pennsylvania, 2008.

Source: Dissertation Abstracts International, Volume: 70-01, Section: B, page: 0296.

Advisers: Amos B. Smith, III; Jeffrey D. Winkler.

Local Notes:

School code: 0175.

ISBN:

9781109008128

Access Restriction:

Restricted for use by site license.