서브메뉴
검색
Addressing the Extremes of Reactivity in Small-Molecule-Catalyzed Stereoselective Glycosylation
Addressing the Extremes of Reactivity in Small-Molecule-Catalyzed Stereoselective Glycosylation
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202103604
- ISBN
- 9798280711297
- DDC
- 547
- 저자명
- Beyer, Peyton.
- 서명/저자
- Addressing the Extremes of Reactivity in Small-Molecule-Catalyzed Stereoselective Glycosylation
- 발행사항
- [Sl] : Harvard University, 2025
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2025
- 형태사항
- 456 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
- 주기사항
- Advisor: Jacobsen, Eric.
- 학위논문주기
- Thesis (Ph.D.)--Harvard University, 2025.
- 초록/해제
- 요약Glycosides play disparate yet essential roles in biology, and as such their study is of great importance to human health. To perform such studies, the stereocontrolled laboratory synthesis of glycosides remains a necessary endeavor. Despite this, the development of general methodology for stereoselective glycosylation is an unmet challenge in organic reaction development. This lack of generality can be attributed, among other reasons, to the incredible range of reactivities present across the various glycosyl donors of biological relevance, owing in turn to their diversity of structures. This is especially problematic for the stereoselective glycosylation of donors that sit at the extremes of reactivity, both high and low, where methodology for glycosylation with biomass sugars is typically not applicable. We aim to address these shortcomings through the development of general catalytic glycosylation protocols that are applicable across donor classes.In Chapter 1, we discuss the relationship between structure and reactivity in chemical glycosylation, highlighting key studies that probe this relationship. We will discuss the stereochemical implications of these structure-reactivity effects, with an emphasis on glycosylation with highly reactive 2-deoxyglycosyl donors and highly unreactive glucuronyl donors. We will then discuss current strategies for the stereoselective preparation of 2-deoxyglycosides and glucuronides, as well as the limitations of these strategies. Finally, we will summarize our research group's development of bis-thiourea-catalyzed stereoselective glycosylation, including key findings, mechanistic studies, and limitations that studies documented in this dissertation aim to address.In Chapter 2, we document the development of bis-thiourea-catalyzed methods for βselective 2-deoxy- and 2,6-dideoxyglucosylations of natural products, carbohydrates, and amino acids. Disarming ester protecting groups were necessary to counter the high reactivity of 2- deoxyglycosyl electrophiles toward non-stereospecific SN1 pathways. Differing catalyst structures were found to be optimal for use of 2-deoxy- and 2,6-dideoxyglycosyl donors. Alcohol and phenol nucleophiles with both base- and acid-sensitive functionalities were compatible with the catalytic protocol, enabling access to a wide array of 2-deoxy-β-O-glucosides.In Chapter 3, we document the successful application of metal-salen catalysis towards β-glucuronidation of alcohols, phenols, and anilines via stereospecific opening of 1,2- anhydroglucuronate electrophiles. The optimized protocol is mild and pH-neutral, enabling βglucuronidation of complex pharmaceuticals and natural products bearing acid-sensitive and Lewis-basic functionality. Kinetic studies are consistent with a transformation that is overall firstorder in catalyst, which contrasts previous metal-salen-catalyzed epoxide opening reactions where second-order rate dependence on catalyst is observed.
- 일반주제명
- Organic chemistry
- 일반주제명
- Inorganic chemistry
- 일반주제명
- Biochemistry
- 키워드
- Glycosides
- 기타저자
- Harvard University Chemistry and Chemical Biology
- 기본자료저록
- Dissertations Abstracts International. 86-12B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
008260126s2025 us c eng d■001000017357814
■00520260202103604
■006m o d
■007cr#unu||||||||
■020 ▼a9798280711297
■035 ▼a(MiAaPQ)AAI32042630
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a547
■1001 ▼aBeyer, Peyton.▼0(orcid)0000-0001-7002-6730
■24510▼aAddressing the Extremes of Reactivity in Small-Molecule-Catalyzed Stereoselective Glycosylation
■260 ▼a[Sl]▼bHarvard University▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a456 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-12, Section: B.
■500 ▼aAdvisor: Jacobsen, Eric.
■5021 ▼aThesis (Ph.D.)--Harvard University, 2025.
■520 ▼aGlycosides play disparate yet essential roles in biology, and as such their study is of great importance to human health. To perform such studies, the stereocontrolled laboratory synthesis of glycosides remains a necessary endeavor. Despite this, the development of general methodology for stereoselective glycosylation is an unmet challenge in organic reaction development. This lack of generality can be attributed, among other reasons, to the incredible range of reactivities present across the various glycosyl donors of biological relevance, owing in turn to their diversity of structures. This is especially problematic for the stereoselective glycosylation of donors that sit at the extremes of reactivity, both high and low, where methodology for glycosylation with biomass sugars is typically not applicable. We aim to address these shortcomings through the development of general catalytic glycosylation protocols that are applicable across donor classes.In Chapter 1, we discuss the relationship between structure and reactivity in chemical glycosylation, highlighting key studies that probe this relationship. We will discuss the stereochemical implications of these structure-reactivity effects, with an emphasis on glycosylation with highly reactive 2-deoxyglycosyl donors and highly unreactive glucuronyl donors. We will then discuss current strategies for the stereoselective preparation of 2-deoxyglycosides and glucuronides, as well as the limitations of these strategies. Finally, we will summarize our research group's development of bis-thiourea-catalyzed stereoselective glycosylation, including key findings, mechanistic studies, and limitations that studies documented in this dissertation aim to address.In Chapter 2, we document the development of bis-thiourea-catalyzed methods for βselective 2-deoxy- and 2,6-dideoxyglucosylations of natural products, carbohydrates, and amino acids. Disarming ester protecting groups were necessary to counter the high reactivity of 2- deoxyglycosyl electrophiles toward non-stereospecific SN1 pathways. Differing catalyst structures were found to be optimal for use of 2-deoxy- and 2,6-dideoxyglycosyl donors. Alcohol and phenol nucleophiles with both base- and acid-sensitive functionalities were compatible with the catalytic protocol, enabling access to a wide array of 2-deoxy-β-O-glucosides.In Chapter 3, we document the successful application of metal-salen catalysis towards β-glucuronidation of alcohols, phenols, and anilines via stereospecific opening of 1,2- anhydroglucuronate electrophiles. The optimized protocol is mild and pH-neutral, enabling βglucuronidation of complex pharmaceuticals and natural products bearing acid-sensitive and Lewis-basic functionality. Kinetic studies are consistent with a transformation that is overall firstorder in catalyst, which contrasts previous metal-salen-catalyzed epoxide opening reactions where second-order rate dependence on catalyst is observed.
■590 ▼aSchool code: 0084.
■650 4▼aOrganic chemistry
■650 4▼aInorganic chemistry
■650 4▼aBiochemistry
■653 ▼aGlucuronyl donors
■653 ▼aStereocontrolled laboratory synthesis
■653 ▼aGlycosides
■690 ▼a0490
■690 ▼a0488
■690 ▼a0487
■71020▼aHarvard University▼bChemistry and Chemical Biology.
■7730 ▼tDissertations Abstracts International▼g86-12B.
■790 ▼a0084
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17357814▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
