(-)-Bisezakyne A 의 전합성과 구조 재교정
Asymmetric Total Synthesis and Structure Revision of (-)-Bisezakyne A
- 주제(키워드) (−)-bisezakyne A , 2 , 5-disubstituted-THF , intramolecular amide enolate alkylation , total synthesis
- 발행기관 아주대학교
- 지도교수 김형수
- 발행년도 2019
- 학위수여년월 2019. 2
- 학위명 박사
- 학과 및 전공 일반대학원 약학과
- 실제URI http://www.dcollection.net/handler/ajou/000000028783
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Functionalized tetrahydrofurans (THFs) constitute key structural features of biologically interesting natural products exhibiting significant various pharmacological activities including anticancer, antiviral, antibiotic and antifungal activities (Figure 1). In particular, 2,5-cis- or -trans disubstituted-THFs are found in a wide range of complex natural products which have been largely attracted from synthetic community culminating the development of a number of methodologies. The total synthesis of proposed (−)-bisezakyne A and revised (−)-bisezakyne A have been accomplished in 15 steps for longest sequence from commercially available hexa-1,5-dien-3-ol with an overall yields of 6.8% and 3.7%, respectively. Highlight of the synthesis include the IAEA (intramolecular amide enolate alkylation) for steroselective synthesis of 2,3-cis-2,5-cis-tetrahydrofuran and 2,3-cis-2,5-trans-tetrahydrofuran and the Nakata’s halogenation protocol. In addition, our synthesis unambiguously confirmed the absolute configuration of the natural (−)-bisezakyne A.
more목차
I. Introduction 1
I.1 Significance of Tetrahydrofuran Skeleton in Nature 1
I.2. Tetrahydrofuran Skeleton in Nature Products 2
I.2.1. Mono-THFs 2
I.2.2. Fused Bis-THFs 5
I.2.3. Adjacent Bis-THFs 6
I.2.4. Non-Adjacent Bis-THFs 8
I.2.5. THF-Containing Macrolides 11
I.2.6. Mono-THF fused with Medium-Sized Ether Ring 14
I.3. Stereoselective Construction of 2,5-Disubstituted THF Skeletons by CarbonCarbon Bond-Forming Cyclization in Total Synthesis of Natural Products 17
I.3.1. Overmans Tandem Prins/Pinacol Reaction for Stereoselective Construction of 2,5-Disubstituted THF Skeletons 20
I.3.2. Lees Radical Reaction for Stereoselective Construction of 2,5-Disubstituted THF Skeletons. 24
II. Results and discussion 33
II.1. Previous Studies 33
II.1.1. Previous Studies On Divergent Construction of 2,5-cis- and 2,5-trans-Disubstituted THFs 33
II.1.2. Previous Results On Divergent Construction of 2,5-cis- and 2,5-trans-Disubstituted THFs by Intramolecular Amide Enolate or Nitrile Anion Alkylation. 34
II.1.3. Protecting Group-Dependent Stereodivergent Intramolecular Amide Enolate Alkylation. 38
II.2. Total Synthesis of Proposed Structure of ()-Bisezakyne A 49
III. Conclusions 72
IV. Experimentals 73
V. References 166
