Part 1. Studies Toward the Total Synthesis of Neaumycin B. Part 2. Synthesis of ortho-halogen-substituted Aryl(alkynyl)phosphinates via three-component coupling reaction.
- 주제어 (키워드) Organic chemistry , total synthesis , methodology
- 발행기관 서강대학교 일반대학원
- 지도교수 이덕형
- 발행년도 2025
- 학위수여년월 2025. 2
- 학위명 박사
- 학과 및 전공 일반대학원 화학과
- 실제 URI http://www.dcollection.net/handler/sogang/000000079618
- UCI I804:11029-000000079618
- 본문언어 영어
- 저작권 서강대학교 논문은 저작권 보호를 받습니다.
초록 (요약문)
Part 1. Studies Toward the Total Synthesis of Neaumycin B. Neaumycin, a compound with the unprecedented structure such as a 30-membered macrolide skeleton featuring an internal diester bridge, was first isolated from the soil- dwelling Steptomyces sp. NEAU-x211 by Shen and co-workers in 2012. Subsequently, Fenical and coworkers isolated Neaumycin B from the culture broth of Micromonospora sp. (strain CNY-010) and proposed the full stereostructure of Neaumycin B by integration of genomic data with its relationship to natural product biosynthesis and spectroscopic data in 2018. Synthesis of the C21-C41 fragment for the reported structure of Neaumycin B was accomplished in 29 steps. Aldehyde was synthesized from the commercially available (S)- Roche ester in 10 steps using stereoselective allylation and Brown anti-crotylation as key steps. Ketone was synthesized from the known oxazolidinone in 18 steps utilizing Evan diastereoselective alkylation, Evans-syn-aldol reaction, hydroxy-group directed epoxidation, and (S)-CBS reduction as key steps. Finally, boron-mediated acetate aldol reaction of aldehyde and ketone led to the synthesis of C21-C41 fragment for the reported structure of Neaumycin B. Part 2. Synthesis of ortho-halogensubstituted Aryl(alkynyl)phosphinates via three-component coupling reaction A operationally simple, high efficient, and metal-free method for synthesizing ortho-halogen-substituted aryl(alkynyl)phosphinates was developed by a three component coupling reaction utilizing arynes, phosphites, and haloalkynes. In this reaction, the aryl anion, generated from the nucleophilic addition of phosphite to aryne, directly attacked halogen of the haloalkyne. The reaction proceeded efficiently with broad substrate scope and excellent functional group compatibility, yielding products with significant utility in natural product synthesis, medicinal chemistry, and materials science.
more초록 (요약문)
Part 1. Studies Toward the Total Synthesis of Neaumycin B. 네우마이신은 내부에 diester bridge 를 특징으로 하는 30 각형의 마크롤라이드 골격을 가진 전례 없는 구조의 화합물로, 2012 년 Shen 그룹에 의해 토양에 서식하는 Steptomyces sp. NEAU-x211 에서 처음 분리되었다. 이후 Fenical 연구팀은 2018 년 Micromonospora sp. (strain CNY-010)의 배양액에서 네우마이신 B 를 분리하고, 유전체 데이터와 천연물의 생합성의 관계 및 분광 데이터를 종합하여 네우마이신 B 의 입체구조를 제안하였다. 네우마이신 B 의 보고된 구조에 대한 C21-C41 조각의 합성은 29 단계에 걸쳐 완료하였다. 알데하이드는 상업적으로 구매 가능한 (S)-Roche ester 로부터 입체 선택적인 알릴화 반응과 Brown 안티-크로틸화를 주요 반응으로 10 단계에 걸쳐 합성하였다. 케톤은 Evans diastereoselective alkylation, Evans syn-알돌반응, hydroxy-group directed 에폭시화, (S)-CBS 환원반응을 주요 반응으로 18 단계에 걸쳐 합성하였다. 최종적으로, 알데하이드와 케톤의 boron-mediated acetate aldol 반응으로 보고된 구조의 네우마이신 B 의 C21-C41 조각의 합성을 완료하였다. Part 2. Synthesis of ortho-halogensubstituted Aryl(alkynyl)phosphinates via three-component coupling reaction 아린 (Aryne), 포스파이트 (Phosphite), 할로알카인 (haloalkyne)을 이용한 3성분 결합 반응으로 오쏘 위치에 할로젠이 치환된 아릴(알카닐)포스피네이트의 합성법을 개발하였다. 이 합성법은 간단하고 효율적인 한 단계 반응이고, 금속이 필요 없으며, 다양한 종류의 작용기가 치환된 알카인, 포스파이트, 벤자인에서도 안정적으로 목표 화합물을 합성할 수 있다. 탄소와 포스핀의 결합, 탄소와 할로젠 결합을 동시에 도입하는 이 합성법은 천연물 전합성, 의약화학 및 소재 분야에서의 다양한 응용성을 입증하였다.
more목차
Part 1. Studies Toward the Total Synthesis of Neaumycin B.
1. Introduction 3
2. Results & Discussion 5
2-1. Retrosynthetic analysis of fragment 5
2-2. Revised Retrosynthetic analysis of fragment4 8
2-3. Synthesis of fragment4 18
2-4. Reported structure of Neaumycin B(X) 21
3. Conclusion 23
4. Experimental Section 24
4-1. General Information 24
4-2. Experimental Procedure and Characterization Data 25
5. References 25
Part 2. Synthesis of ortho-halogensubstituted Aryl(alkynyl)phosphinates via three-component coupling reaction 58
1. Introduction 58
2. Results & Discussion 60
2-1. Reaction optimization 60
2-2. Substrate scope of aryl-substituted bromoalkynes 62
2-3. Substrate scope of aliphatic group-substituted bromoalkynes 64
2-4. Substrate scope of phosphites 66
2-5. Substrate scope of arynes 67
2-6. Substrate scope of haloalkynes 69
2-7. Synthetic application 71
2-8. Proposed mechanism 72
3. Conclusion 74
4.Experimental Section 75
4-1. General Information 75
4-2. Experimental Procedure and Characterization Data 76
5. References 127
