자료유형  

 학위논문

Control Number  

0017161827

International Standard Book Number  

9798384453253

Dewey Decimal Classification Number  

540

Main Entry-Personal Name  

Hayward Cooke, Jack.

Publication, Distribution, etc. (Imprint  

[S.l.] : University of California, Berkeley., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

373 p.

General Note  

Source: Dissertations Abstracts International, Volume: 86-03, Section: B.

General Note  

Advisor: Sarpong, Richmond.

Dissertation Note  

Thesis (Ph.D.)--University of California, Berkeley, 2024.

Summary, Etc.  

요약Herein, I describe our synthetic studies toward the aphidicolin family of diterpenoid natural products and our synthesis of the isocyanosesquiterpene natural products 9-isocyanopupukeanane and 2-isocyanoallopupukeanane.Chapter 1 reviews the isolation, biosynthesis, biological activity, and previous syntheses of aphidicolin, as well as our proposal to synthesize aphidicolin and its more oxygenated congeners. This includes a detailed discussion of aphidicolin's biological mode of action and our structural hypothesis for the development of aphidicolin-based therapeutics using the recently isolated congeners.Chapter 2 describes our various synthetic investigations toward constructing the aphidicolin scaffold. During these studies, we developed a pseudo-desymmetrization of a cyclobutyl pronucleophile using an allyl electrophile and subsequently established condition-dependant formation of linear or crossed intramolecular [2+2]-photocycloaddition adducts. This culminated in the formation of a late-stage pentacyclic intermediate containing the embedded aphidicolin scaffold.Chapter 3 reviews the isolation, biosynthesis, biological activity, and previous syntheses of various pupukeanane natural products-specifically, 9-isocyanopupukeanane and 2-isocyanoallopupukeanane. In addition, previous synthetic efforts performed in our group toward this family are described, culminating in a 10-step enantiospecific formal synthesis of 2-isocyanoallopupukeanane. This also includes computationally guided investigations into the "contra-biosynthetic" rearrangement of the allopupukeanane core to the pupukeanane core, which was achieved by the formation of a sultone.Chapter 4 details our subsequent synthetic investigations toward 9-isocyanopupukeanane, leveraging higher-order magnesiates to open the pupukeanyl sultone and introduce a functional handle to mediate desulfurization. This culminated in a 15-step enantiospecific formal synthesis of 9-isocyanopupukeanane, demonstrating the utility and feasibility of "contra-biosynthetic" strategies in total synthesis.

Subject Added Entry-Topical Term  

Chemistry.

Subject Added Entry-Topical Term  

Biochemistry.

Subject Added Entry-Topical Term  

Analytical chemistry.

Subject Added Entry-Topical Term  

Organic chemistry.

Index Term-Uncontrolled  

2-isocyanoallopupukeanane

Index Term-Uncontrolled  

9-isocyanopupukeanane

Index Term-Uncontrolled  

Aphidicolin

Index Term-Uncontrolled  

Natural products

Index Term-Uncontrolled  

Total synthesis

Added Entry-Corporate Name  

University of California, Berkeley Chemistry

Host Item Entry  

Dissertations Abstracts International. 86-03B.

Electronic Location and Access  

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Control Number  

joongbu:654592