목차

I. Introduction 1
I.1. 3-Oxygenated Tetrahydrofuranoids Natural Products 2
I.1.1. Mono-THFs 2
I.1.2. Fused Bis-THFs 8
I.1.3. Adjacent Bis-THFs 10
I.1.4. THF-Containing Macrolides. 13
I.1.5. Mono-THF Fused with Medium-Sized Ether Ring 15
I.2. Previous Synthesis of Adjacent Bis-THF Acetogenins. 18
I.2.1. Marshall's Total Synthesis of (+)-Trilobin 18
I.2.2. Sinha and Keinan's Total Synthesis of (+)-Trilobacin 20
I.2.3. Sinha and Keinan's Total Synthesis of (+)-Asimicin 22
I.2.4. Borhan's Synthesis of 17-Hydroxy Annonaceous Acetogeinin Mucoxin 25
II. Results and Discussions 28
II.1. Previous Studies on Amide Enolate Alkylation 28
II.1.1. Kim's Divergent Construction of 2,5-cis- and 2,5-trans- Disubstituted THFs by Intramolecular Amide Enolate or Nitrile Anion 28
II.1.2. Kim's Protecting Group-Dependent Intermolecular Amide Enolate Alkylation 31
II.2. Kim's Intramolecular Protecting Group-Dependent Amide Enolate Alkyation for Tetrahydrofuran 33
II.2.1. Substrate Scope for IAEA Reaction 34
II.2.2. Kim's Total Synthesis of C19 Nematocidal Tetrahydrofuranoids Oxylipids 38
II.2.3. Kim's Total Synthesis and Structure revision of (‒)-Bisezakyne A 47
II.2.4. Kim's Total Synthesis of (+)-Laurenidificin and (+)-Aplysiallene 52
II.3. Total Synthesis C37 Annonaceous Acetogenin (‒)-Asimitrin (1a) 58
II.3.A. (‒)-Asimitrin (1a) 58
II.3.B. Total Synthesis of C37 Annonaceous Acetogenin (‒)-Asimitrin (1a) 61
II.3.1. Retrosynthetic Plan 62
II.3.2. Construction of Key 17-Hydroxy-16,17-erythro-16,17-trans-THF 6 64
II.3.3. Construction of Key 17-Hydroxy-16,17-erythro-16,19-trans-THF 6 by Intramolecular Amide Enolate Alkylation 66
II.3.4. Construction of Key 17-Hydroxy-16,17-erythro-16,19-trans-20, 23-trans Adjacent Bis-THF 3a 67
II.3.5. Construction of Homoallylic Alcohol 2a by Keck Allylation 73
II.3.6. Keck Allylation of 17-OTIPS Bis-THF Alcohol II-3-21 75
II.3.7. Completion of the Total Synthesis of (−)-Asimitrin (1a) 80
II.3.C. Synthesis of 16,19-trans/20,23-cis, 16,19-cis/20,23-cis and 16,19-cis/ 20,23-trans Diastereomers of (‒)-Asimitrin (1a) 82
II.3.8. Construction of Key Intermediate 5b-5d 86
II.3.9. Construction of Key 17-Hydroxy-16,17-erythro-16,19-trans 20, 23-cis Adjacent Bis-THF 3b 88
II.3.10. Construction of Homoallylic Alcohol 2b by Keck Allylation 90
II.3.11. Completion of the Total Synthesis of 16,19-trans-20,23-cis Adjacent Bis-THF Asimitrin Diastereomer (1b) 92
II.3.12. Construction of Key 17-Hydroxy-16,17-erythro-16,19-cis-20,23- cis Adjacent Bis-THF 3c 94
II.3.13. Construction of Homoallylic Alcohol 2c by Keck Allylation 96
II.3.14. Completion of the Total Synthesis of 16,19-cis-20,23-cis Adjacent Bis-THF Asimitrin Diastereomer (1c) 98
II.3.15. Construction of Key 17-Hydroxy-16,17-erythro-16,19-cis- 20,23-trans Adjacent Bis-THF 3d 100
II.3.16. Construction of Homoallylic Alcohol 2d by Keck Allylation 102
II.3.17. Completion of the Total Synthesis of 16,19-cis-20,23-trans Adjacent Bis-THF Asimitrin Diastereomer (1d) 104
II.3.18. Improved Route to Key 17-Hydroxy-16,17-erythro-16,19-trans- 20,23-trans Adjacent Bis-THF 3a 106
III. Conclusion 110
IV. Experimentals 111
IV.1. Chelate-Controlled IAEA Reaction 112
IV.1.1. Construction of Intermediate 7 for IAEA Reaction 112
IV.1.2. Construction of 17-Hydroxy-16,17-erythro-16,19-trans-THF 6through Chelate-Controlled IAEA Reaction 117
IV.2. Initial Route for Total Synthesis C37 Annonaceous Acetogenin (‒)-Asimitrin (1a) 118
IV.2.1. Initial Construction of Key C(15)-C(34) Adjacent Bis-THF 3a Preparation of Ketone II-3-3 118
IV.2.2. Keck Allylation of 17-OPMB Bis-THF Aldehyde II-3-15 130
IV.3. Keck Allylation of 17-OTIPS Bis-THF Aldehyde II-3-21 136
IV.3.1. Keck Allylation of 17-OTIPS Aldehyde II-3-22 136
IV.3.2. Confirmation of C(15)/C(16)-threo Configuration in II-3-23 by Chemical Correlation Method 142
IV.4. Completion of Total Synthesis of (‒)-Asimitrin (1a) 145
IV.5. Initial Route for Total Synthesis C37 Annonaceous Acetogenin Asimitrin Diastereomer (1b) 152
IV.5.1. Synthesis of Intermediate of Asimitrin Diastereomers by Epimerization and Reduction 152
IV.5.2. Initial Construction of Key C(15)-C(34) Adjacent Bis-THF 3b 153
IV.5.3. Keck Allylation of 17-OPMB Bis-THF Aldehyde II-3-38 160
IV.5.4. Completion of Total Synthesis of Asimitrin (1b) 166
IV.6. Initial Route for Total Synthesis C37 Annonaceous Acetogenin Asimitrin Diastereomer (1c) 170
IV.6.1. Synthesis of Intermediate of Asimitrin Diastereomers by Epimerization and Reduction 170
IV.6.2. Construction of Key C(15)-C(34) Adjacent Bis-THF 3c 173
IV.6.3. Keck Allylation of 17-OPMB Bis-THF Aldehyde II-3-52 180
IV.6.4. Completion of Total Synthesis of Asimitrin (1c) 185
IV.7. Initial Route for Total Synthesis C37 Annonaceous Acetogenin Asimitrin Diastereomer (1d) 189
IV.7.1. Initial Construction of Key C(15)-C(34) Adjacent Bis-THF 3d 189
IV.7.2. Keck Allylation of 17-OPMB Bis-THF Aldehyde II-3-65 196
IV.7.3. Completion of Total Synthesis of Asimitrin (1d) 202
IV.8. Improved Route to Construction of 17-Hydoxy-16,19-trans- 20,23-trans Adjacent Bis-THF 3a 209
IV.8.1. Improved Route to Key C(15)-C(34) Adjacent Bis-THF 3a 209
IV.9. 1H NMR, 13C NMR Spectra 216
V. References 320