Tetrahydroxanthones are a large class of natural products that contain a partially reduced xanthone moiety. These compounds exist in both monomeric and dimeric forms in nature. A concise retro-biomimetic synthetic approach to monomeric tetrahydroxanthone natural products has been developed. The key transformation involves vinylogous addition of siloxyfurans to benzopyryliums to access chromone lactone precursors which is followed by late-stage Dieckmann cyclization to the tetrahydroxanthone core. Application of this methodology led to efficient syntheses of blennolides B, C, and its stereoisomer epi-blennolide C.
Synthetic efforts towards dimeric tetrahydroxanthones, including 2,2'-biaryl dimer secalonic acid D, have been pursued as well. We developed an efficient kinetic resolution using homobenzotetramisole (HBTM) catalysis to obtain enantiopure tetrahydroxanthones. The development of a mild, copper-mediated dimerization of stannyl tetrahydroxanthones also allowed access to enantiopure 2,2'-linked dimeric tetrahydroxanthones including secalonic acids A and D.
After successful syntheses of secalonic acids A and D, we also applied the methodologies developed towards a synthesis of the axially chiral dimer rugulotrosin A. An enantiopure monomer was prepared in gram-scale by applying our previously developed methodology. The atropselective synthesis of rugulotrosin A was achieved via a one-pot Sukuzi dimerization with chiral palladium precatalyst. A rationale for point-to-axial chirality transfer observed in the key dimerization step has been developed. This key transformation led to the successful 7-step syntheses of rugulotrosin A, its enantiomer, and the atropisomer.
Finally, we further exploited the kinetic resolution using homobenzotetramisole catalysts which successfully led to a unified strategy for syntheses of both the 2,4'-linked and 4',4'-linked secalonic acid derivatives. The isomerization properties of 2,2'-linked, 2,4'-linked, and 4,4'-linked secalonic acids was also studied in an effort to understand the "shapeshifting" properties of the dimeric tetrahydroxanthone family.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/15654 |
| Date | 12 March 2016 |
| Creators | Qin, Tian |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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