서브메뉴
검색
Synthetic Studies Toward the Aphidicolin Family and Total Synthesis of Pupukeanane Natural Products Using a "Contra-biosynthetic" Strategy
Synthetic Studies Toward the Aphidicolin Family and Total Synthesis of Pupukeanane Natural Products Using a "Contra-biosynthetic" Strategy
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211151450
- ISBN
- 9798384453253
- DDC
- 540
- 서명/저자
- Synthetic Studies Toward the Aphidicolin Family and Total Synthesis of Pupukeanane Natural Products Using a Contra-biosynthetic Strategy
- 발행사항
- [Sl] : University of California, Berkeley, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 373 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-03, Section: B.
- 주기사항
- Advisor: Sarpong, Richmond.
- 학위논문주기
- Thesis (Ph.D.)--University of California, Berkeley, 2024.
- 초록/해제
- 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.
- 일반주제명
- Chemistry
- 일반주제명
- Biochemistry
- 일반주제명
- Analytical chemistry
- 일반주제명
- Organic chemistry
- 키워드
- Aphidicolin
- 키워드
- Natural products
- 키워드
- Total synthesis
- 기타저자
- University of California, Berkeley Chemistry
- 기본자료저록
- Dissertations Abstracts International. 86-03B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
008250123s2024 us c eng d■001000017161827
■00520250211151450
■006m o d
■007cr#unu||||||||
■020 ▼a9798384453253
■035 ▼a(MiAaPQ)AAI31296720
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a540
■1001 ▼aHayward Cooke, Jack.
■24510▼aSynthetic Studies Toward the Aphidicolin Family and Total Synthesis of Pupukeanane Natural Products Using a "Contra-biosynthetic" Strategy
■260 ▼a[Sl]▼bUniversity of California, Berkeley▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a373 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-03, Section: B.
■500 ▼aAdvisor: Sarpong, Richmond.
■5021 ▼aThesis (Ph.D.)--University of California, Berkeley, 2024.
■520 ▼aHerein, 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.
■590 ▼aSchool code: 0028.
■650 4▼aChemistry
■650 4▼aBiochemistry
■650 4▼aAnalytical chemistry
■650 4▼aOrganic chemistry
■653 ▼a2-isocyanoallopupukeanane
■653 ▼a9-isocyanopupukeanane
■653 ▼aAphidicolin
■653 ▼aNatural products
■653 ▼aTotal synthesis
■690 ▼a0485
■690 ▼a0487
■690 ▼a0486
■690 ▼a0490
■71020▼aUniversity of California, Berkeley▼bChemistry.
■7730 ▼tDissertations Abstracts International▼g86-03B.
■790 ▼a0028
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17161827▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
