Chapter 1. Part 1: Novel Synthesis and Biological Evaluation of1,5-Linked D-Mannoseptanosides. Part 2: Synthesis ofD-Glucoseptanosides Chapter 2. Biomimetic Total Synthesis of theProposed Structure of ent-Muzitone Open Access
Boone, Matthew Allen (2009)
Abstract
Chapter 1. Part 1: Novel Synthesis and Biological Evaluation of 1,5-Linked D-Mannoseptanosides. Part 2: Synthesis of D-Glucoseptanosides Part 1. Using the tungsten-catalyzed cycloisomerization of an appropriately protected alkynyl alcohol, highly functionalized seven-membered ring (septanose) glycals were synthesized. We used dimethyldioxirane (DMDO) glycal epoxidation/epoxide opening to construct septanose sugars with D- manno absolute configuration, which were glycosylated to give the first known 1,5-linked D-mannoseptanoside mono-, di-, and trisaccharides. These unnatural sugars were found to be innocuous to α-mannosidase-catalyzed hydrolysis. Thus, we believe these unique carbohydrate structures have potential application as biomaterials or drug delivery vehicles. Part 2. Using a known strategy of protecting group manipulation of a hexose sugar, we have synthesized a variety of D-glucoseptanose substrates. Our ultimate goal was to construct higher order oligosaccharides composed of D-glucoseptanose monomer units. While that goal remained elusive, we gained much insight into the reactivity patterns of these substrates, which will be insightful in future studies.
Chapter 2. Biomimetic Total Synthesis of the Proposed Structure of ent-Muzitone Muzitone, a marine sponge-derived polycyclic ether triterpenoid natural product, was synthesized using a bioinspired strategy. Starting from a C30 squalene-like precursor, we successfully used tandem biomimetic cyclizations of epoxy-ene substrates to construct ent-muzitone. This synthetic investigation revealed that the structural and/or stereochemical assignment of muzitone was incorrect.
Table of Contents
Table of Contents Chapter 1. Part 1: Novel Synthesis and Biological Evaluation of 1,5-Linked D-Mannoseptanosides. Part 2: Synthesis of D-Glucoseptanosides 1.1. Introduction and Background...2
1.1.1. Potential applications of septanose carbohydrates...2 1.1.2. Enzyme recognition of septanose carbohydrates...3 1.1.3. Synthetic approaches to septanose carbohydrates...4 1.1.4. McDonald's tungsten hexacarbonyl (W(CO)6)-catalyzed synthesis of septanose glycals...11
1.2. Results and Discussion...17
1.2.1. Synthesis of 1,5-linked D-mannoseptanose mono-, di-, and trisaccharides...17 1.2.2. Synthesis of D-glucoseptanoses...26
1.3. Experimental Details...32
1.3.1. 1,5-D-Mannoseptanosides...32 1.3.2. D-Glucoseptanosides...99
Chapter 2. Biomimetic Total Synthesis of the Proposed Structure of ent-Muzitone 2.1. Introduction and Background...125
2.1.1. Biogenetic origin of squalene-derived natural products...125
2.1.1.1. Importance of the biomimetic synthesis of polycyclic isoprenoid natural products; Stereospecificity of polycyclization cascades...125 2.1.1.2. Biomimetic total synthesis of squalene-derived natural products featuring polycyclization cascades: experimental evidence for the biogenesis of squalene-derived natural products...128
2.1.2. Biomimetic synthesis of polycyclic ether natural products...131
2.1.2.1. Biogenetic origin of polycyclic ether natural products...131 2.1.2.2. Methodologies for the construction of polycyclic ether motifs...134 2.1.2.3. Biomimetic total syntheses involving epoxide-opening cascades en route to polycyclic ether natural products...138
2.1.3. McDonald's synthetic efforts towards squalene-derived polycylic ether natural products...141
2.1.3.1. Postulated biogenesis of muzitone (49)...148
2.2. Biomimetic synthesis of ent-muzitone (ent-49) from a squalene-like precursor...151
2.2.1. Retrosynthesis...151 2.2.2. Results and Discussion...152
2.3. Experimental Details...172 Appendix 1. Total synthesis of (3R,6R,7R,18R,19R,22R)-squalene tetraepoxide A1.1. Introduction and Background...289 A1.2. Results and Discussion...290 A1.3. Experimental Details...294 References...304
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Chapter 1. Part 1: Novel Synthesis and Biological Evaluation of1,5-Linked D-Mannoseptanosides. Part 2: Synthesis ofD-Glucoseptanosides Chapter 2. Biomimetic Total Synthesis of theProposed Structure of ent-Muzitone () | 2018-08-28 12:41:34 -0400 |
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