Direct approaches to natural product synthesis

In this dissertation, we have investigated direct routes to several biologically important natural products.;Chapter 1 describes a concise construction of core skeleton of malibatol A, employing a novel benzofuran formation methodology and a regio- and stereoselective 7-membered ring formation via Lewis acid catalyzed epoxide ring opening as crucial steps.;Chapter 2 describes direct approaches to isoflavanquinones utilizing radical addition to quinones. Three main strategies were presented and were compared to generate radicals from the corresponding precursors.;Chapter 3 describes a direct entry to erogorgiaene, naturally occurring potent antitubercular agent, featuring a regioselective metal-halogen exchange and a 6-exo-trig radical cyclization as key transformations.;Chapter 4 describes synthetic studies towards antitubercular benzoxazole alkaloids. The core tricyclic skeleton of the originally proposed structures of these natural products was synthesized using an intermolecular Diels-Alder reaction as a key step

A Direct Synthesis of O-Methyl Claussequinone

The reaction of a chromene with BH3 followed by treatment with benzoquinone and air is the key step in a direct entry to O-methyl claussequinone

Direct approaches to natural product synthesis

In this dissertation, we have investigated direct routes to several biologically important natural products.;Chapter 1 describes a concise construction of core skeleton of malibatol A, employing a novel benzofuran formation methodology and a regio- and stereoselective 7-membered ring formation via Lewis acid catalyzed epoxide ring opening as crucial steps.;Chapter 2 describes direct approaches to isoflavanquinones utilizing radical addition to quinones. Three main strategies were presented and were compared to generate radicals from the corresponding precursors.;Chapter 3 describes a direct entry to erogorgiaene, naturally occurring potent antitubercular agent, featuring a regioselective metal-halogen exchange and a 6-exo-trig radical cyclization as key transformations.;Chapter 4 describes synthetic studies towards antitubercular benzoxazole alkaloids. The core tricyclic skeleton of the originally proposed structures of these natural products was synthesized using an intermolecular Diels-Alder reaction as a key step.</p

Synthetic Approach to Malibatol A

A synthetic approach to malibatol A featuring a novel benzofuran synthesis is described.Reprinted (adapted) with permission from Organic Letters; 5(8); 1191-1192. Doi: 10.1021/ol027574o. Copyright 2003 American Chemical Society.</p

A Direct Synthesis of O-Methyl Claussequinone

The reaction of a chromene with BH3 followed by treatment with benzoquinone and air is the key step in a direct entry to O-methyl claussequinone.Reprinted (adapted) with permission from The Journal of Organic Chemistry; 68(11); 4517-4518. Doi: 10.1021/jo030026j. Copyright 2003 American Chemical Society.</p

Total Synthesis of Brazilin

Described herein is a highly efficient total synthesis of brazilin from commercially available starting materials in 9 steps with 70% overall yield. Mitsunobu coupling followed by In­(III)-catalyzed alkyne–aldehyde metathesis allowed for rapid construction of brazilin core skeleton in quantitative yield. Subsequent modulation of oxidation levels and acid-catalyzed cyclization led to the trimethyl ether of brazilin. Asymmetric dihydroxylation of the key intermediate was also demonstrated, which would permit asymmetric access to (+)-brazilin

Symmetry-based approach to oligostilbenoids: Rapid entry to viniferifuran, shoreaphenol, malibatol A, and diptoindonesin G

The recognition of the local symmetric image within benzofuran-based natural oligostilbenoids guided us to design a modular synthetic approach to these molecules by utilizing a three-step sequence consisting of Sonogashira coupling, iodocyclization, and Suzuki coupling. During our synthesis, the relative reactivities of ester, aldehyde, and alkoxy groups on the same aryl ring toward the neighboring alkyne in the iodine-mediated cyclization reactions were explored. Starting from the symmetrical 3,5-dimethoxybenzyl alcohol, this route allowed rapid access to 2,3-diarylbenzofuran, a key intermediate to several oligostilbenoid natural products, in good overall yields

Alkyne Carbonyl Metathesis As a Means To Make 4‑Acyl Chromenes: Syntheses of (±)-Deguelin and (±)-Munduserone

A highly convergent synthetic approach to rotenoid natural products is described. Successful pairing of two building blocks for Sonogashira cross-coupling and intramolecular alkyne carbonyl metathesis allows ready access to 4-acylchromene, a key substructure of these natural products, leading to syntheses of (±)-deguelin and (±)-munduserone in high overall yields

Deformylative Intramolecular Hydroarylation: Synthesis of Benzo[<i>e</i>]pyrido[1,2‑<i>a</i>]indoles

Attempted cyclization of indolizines bearing both formyl and alkyne groups under acid catalysis provided benzo­[<i>e</i>]­pyrido­[1,2-<i>a</i>]­indoles with an aryl substituent at the C6 position as major products, along with the expected C5-acylated benzo­[<i>e</i>]­pyrido­[1,2-<i>a</i>]­indoles as minor ones, which resulted from preferential deformylative intramolecular hydroarylation instead of intended alkyne-carbonyl metathesis

Cycloaromatization Approach to Polysubstituted Indolizines from 2‑Acetylpyrroles: Decoration of the Pyridine Unit

A new synthetic route to indolizines with various substituents on the pyridine moiety was developed by utilizing a facile cycloaromatization of 2-acetylpyrrole derivatives. Without isolation, the resulting intermediates were allowed to react with various electrophiles to afford a range of indolizines. In particular, Suzuki–Miyaura cross-coupling of <i>O</i>-triflates with (hetero)­arylboronic acids permitted introduction of diverse substituents at the C8 position of an indolizine skeleton