UVM Theses and Dissertations
Format:
Print
Author:
Panarese, Joseph David
Dept./Program:
Chemistry
Year:
2012
Degree:
PhD
Abstract:
In 2008, (+)-aspergillide C was isolated from a marine-derived fungus, Aspergillus ostianus. In a biological study, (+)-aspergillide C displayed cytotoxicity (LD₅₀= 2.0 [Greek mu]/mL) against mouse lymphocytic leukemia cells (L1210). An enantioselective formal total synthesis of the macrolide (+)-aspergillide C has been accomplished from (S)-( - )-glyceraldehyde acetonide and the Danishefsky-Kitahara diene. Strategic transformations include a hetero cyclocondensation reaction, Ferriertype addition, and palladium-catalyzed oxidative lactonization to set key stereocenters within the dihydropyran core, followed by fragment coupling via E-selective JuliaKocienski olefination.
A facile aromatization of tetrahydro-[Greek bata]-carbolines with both phenyl and aliphatic substituents at C-I has been accomplished. This oxidation, mediated by 2-iodoxybenzoic acid, occurs at room temperchure in two hours. A library of aromatic [Greek beta]-carbolines has been produced, and this methodology has been utilized in a total synthesis of the marine bis-indole alkaloid eudistomin U.
A successful extension of this method to tetrahydro-[Greek beta]-carbolines with benzyl substituents at C-1 was achieved. The corresponding benzyl-substituted aromatic [Greek beta]-carbolines were obtained in high yield along with a small amount of benzoyl-substituted aromatic [Greek beta]-carbolines. Later, it was found that elemental iodine could facilitate a tandem oxidation process to provide benzoyl-substituted aromatic [Greek beta]-carbolines in high yield. This method was successfully extended to 4-mesyloxybenzyl-substituted tetrahydro-[Greek beta]-carbolines and then applied to the total synthesis of eudistomins Y₁-Y₆.
In 2009, hyrtiocarboline was isolated from the Papua New Guinea marine sponge, Hyrtios reticulatus. It showed selective antiproliferative activity against non-small cell lung (H522-T1), melanoma (MDA-MB-435), and lymphoma (U937) cancer cell lines. Studies toward the synthesis of this [Greek beta]-carboline alkaloid have been performed. The synthesis of a suitable tetrahydro-[Greek beta]-carboline precursor to hyrtiocarboline was explored. Newly developed tandem-oxidation methodology led to the successful production of a C-1 formyl-substituted aromatic [Greek beta]-carboline which can be used in the total synthesis of hyrtiocarboline.
A facile aromatization of tetrahydro-[Greek bata]-carbolines with both phenyl and aliphatic substituents at C-I has been accomplished. This oxidation, mediated by 2-iodoxybenzoic acid, occurs at room temperchure in two hours. A library of aromatic [Greek beta]-carbolines has been produced, and this methodology has been utilized in a total synthesis of the marine bis-indole alkaloid eudistomin U.
A successful extension of this method to tetrahydro-[Greek beta]-carbolines with benzyl substituents at C-1 was achieved. The corresponding benzyl-substituted aromatic [Greek beta]-carbolines were obtained in high yield along with a small amount of benzoyl-substituted aromatic [Greek beta]-carbolines. Later, it was found that elemental iodine could facilitate a tandem oxidation process to provide benzoyl-substituted aromatic [Greek beta]-carbolines in high yield. This method was successfully extended to 4-mesyloxybenzyl-substituted tetrahydro-[Greek beta]-carbolines and then applied to the total synthesis of eudistomins Y₁-Y₆.
In 2009, hyrtiocarboline was isolated from the Papua New Guinea marine sponge, Hyrtios reticulatus. It showed selective antiproliferative activity against non-small cell lung (H522-T1), melanoma (MDA-MB-435), and lymphoma (U937) cancer cell lines. Studies toward the synthesis of this [Greek beta]-carboline alkaloid have been performed. The synthesis of a suitable tetrahydro-[Greek beta]-carboline precursor to hyrtiocarboline was explored. Newly developed tandem-oxidation methodology led to the successful production of a C-1 formyl-substituted aromatic [Greek beta]-carboline which can be used in the total synthesis of hyrtiocarboline.