Stereoselective Total Syntheses of both (+)-2,5-cis- and (+)-2,5-trans- Tetrahydrofuranoid Oxylipids
Stereoselective Total Syntheses of both (+)-2,5-cis- and (+)-2,5-trans- Tetrahydrofuranoid Oxylipids
- 주제(키워드) alkylations , cyclizations , heterocycles , natural products , total synthesis
- 발행기관 아주대학교
- 지도교수 김형수
- 발행년도 2020
- 학위수여년월 2020. 2
- 학위명 박사
- 학과 및 전공 일반대학원 약학과
- 실제URI http://www.dcollection.net/handler/ajou/000000029841
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
The concise, highly stereoselective, substrate-controlled asymmetric total syntheses of both 2,5-trans- and 2,5-cis-tetrahydrofuranoid nematocidal oxylipids from the Australian brown algae Notheia anomala have been accomplished in a stereodivergent fashion. The highly stereoselective intramolecular amide enolate alkylation strategy provides access to both stereoisomers of the 3-hydroxy-2,5- disubstituted tetrahydrofuran core of these marine natural products through chelate and nonchelate control, which is driven by the C(3)-hydroxy protecting group. This approach offers an optional and highly stereoelective access to any of the eight possible stereoisomers of the 2,5-disubstituted-3-oxygenated tetrahydrofuran skeleton, an important structural feature which is present in many biologically active natural products.
more목차
I. Introductions .......................................................................................................... 1
I.1. 3-Oxygenated Tetrahydrofuranoids Natural Products ................................. 2
I.1.1. Mono-THFs ........................................................................................ 2
I.1.2. Fused Bis-THFs .................................................................................. 7
I.1.3. Adjacent Bis-THFs ............................................................................. 9
I.1.4. THF-Containing Macrolides ............................................................ 12
I.1.5. Mono-THF fused with Medium-Sized Ether Ring ........................... 14
I.2. C19 Nematocidal Tetrahydrofuranoids Marine Oxylipids .......................... 17
I.2.1. Introduction: Determination of C19 Nematocidal Tetrahydrofuranoids
Oxylipids.................................................................................................... 17
I.2.2. Biosynthetic Pathway of C19 Nematocidal Tetrahydrofuranoids
Oxylipids.................................................................................................... 19
I.3. Previous Synthesis of C19 Nematocidal Tetrahydrofuranoids Marine
Oxylipids .......................................................................................................... 23
I.3.1. Williams Synthesis of (±)-1a (1984) ................................................ 27
I.3.2. Takano Synthesis of (+)-1a (1985) ................................................... 29
I.3.3. Gurjar Synthesis of (+)-1a (1990) .................................................... 30
I.3.4. Chikashita Synthesis of (+)-1a (1993) ............................................. 31
I.3.5. Wang Synthesis of (+)-1a (1998) ..................................................... 32
I.3.6. Mori Synthesis of (+)-1a (1999) ...................................................... 34
I.3.7. Martin Synthesis of (+)-1a and (+)-1b (2000,2001) ........................ 35
I.3.8. Lowary Synthesis of (+)-1b (2001) .................................................. 37
I.3.9. Yoda Synthesis of (+)-1b (2001) ...................................................... 39
I.3.10. Pradilla Synthesis of (+)-1a (2007, 2009) ...................................... 40
I.3.11. Britton Synthesis of (+)-1a and (+)-1b (2009) ............................... 42
I.3.12. McErlean Synthesis of (−)-1a and (−)-1b (2011) ........................... 44
I.3.13. Spilling Synthesis of (+)-1a and (+)-1b (2012) ............................. 45
I.3.14. Song Synthesis of (+)-1b (2013) .................................................... 47
II. Result and Discussions ....................................................................................... 49
II.1. Previous Studies on Amide Enolate Alkylation ........................................ 49
II.1.1. Kim’s Divergent Construction of 2,5-cis- and 2,5-trans-Disubstituted
THFs by Intramolecular Amide Enolate or Nitrile Anion Alkylation ....... 49
II.1.2. Kim’s Protecting Group-Dependent Intermolecular Amide Enolate
Alkylation .................................................................................................. 51
II.2. Intramolecular Protecting Group-Dependent Amide Enolate Alkylation . 53
II.2.1. Substrate Scope for IAEA Reaction ................................................ 54
II-3. Total Synthesis of C19 Nematocidal Tetrahydrofuranoids Oxylipids 1a and
1b ................................................................................................................ 59
II-3-1. Retrosynthetic Plan ......................................................................... 59
II-3-2. Construction of key 2,5-trans- and 2,5-cis-THF intermediates 3a and
3b ............................................................................................................... 61
II-3-3. Determination the Relative Stereochemistries of IAEA Adducts in
Scheme 25 and 26 by Chemical Correlations ............................................ 69
II-3-4. Construction of 2,3-trans-2,5-trans- and 2,3-trans-2,5-cis-THFs 3c
and 3d ........................................................................................................ 71
II-3-5. Determination the Relative Stereochemistries of IAEA Adducts in
Scheme 31 and 32 by Chemical Correlations ............................................ 75
II-3.6. Completion of the Total Synthesis of 1a and 1b ............................ 77
III. Conclusions ....................................................................................................... 80
IV. Exprimentals ...................................................................................................... 81
V. References ........................................................................................................ 195
