Total syntheses of (±)-dracephalone A and (±)-dracocequinones A and B, progress towards a total synthesis of cassiabudanols A and B, and synthetic studies towards total synthesis of N-oxy-diketopiperazine containing natural products.

In 2022 we reported the first total syntheses of 20-nor-abietanoids (±)-dracocephalone A and (±)-dracocequinones A and B. Our synthesis originally involved an isobenzofuran intramolecular Diels-Alder, a strategy that eventually evolved into a Lewis acid-mediated spirocyclization in a highly diastereoselective fashion. Subsequent trans-decalin formation and a late-stage Suárez oxidation constructed the [3.2.1] oxabicylic core that led to the completion of (±)-dracocephalone A in 10 steps and 8% overall yield from known materials. Brønsted acid-promoted aromatization of a late-stage intermediate, followed by careful oxidations, allowed for the rearrangement to the [2.2.2] oxabicyclic core poised for conversion to (±)-dracocequinones A and B in 13 and 15 steps, respectively, from known materials. An asymmetric synthesis of the cyclopentane portion of Cassiabudanol A and B is described, wherein stereoselective ring contraction under Favorskii conditions was used as the key step from (R)-14-hydroxycarvone derivative. Initial challenges were associated with the scalable preparation of (R)-14-hydroxycarvone. Screening of cyclobutane fragmentation revealed SnCl4 as the most reliable Lewis acid in various scales. Subsequent manipulation of (R)-14-hydroxycarvone set the stage for Favorskii rearrangement albeit mixture of diastereomers. Further functional group interconversions not only allowed for the separation of diastereomers but set the stage for the future strategy that includes intramolecular furan Diels-Alder. In 2021 we completed the asymmetric total synthesis of (+)-raistrickindole A in 9 steps and overall 2% yield from known materials, featuring a diastereoselective intermolecular nitroso Diels-Alder (NDA) cycloaddition as the key step in constructing the oxazine core. In utilizing (+)-raistrickindole A as a late-stage intermediate to target (-)-haenamindole, optimization efforts of the route, especially Mukaiyama hydration and diketopiperazine (DKP) formation steps, are discussed to achieve overall 13% yield. An asymmetric synthesis of the tricyclic core of [2.2.3]-Epidithiodiketopiperazines is described. The key step features a diastereoselective intramolecular NDA reaction of the cyclopentadiene adduct intermediate derived from (-)-quinic acid. Attempts to install the tertiary alcohol via a diastereoselective epoxidation from the NDA cycloadduct, as well as a proposed synthetic plan, are discussed.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Doctoral

Grantor

Baylor University.

Year dc:date.issued

2023

Author dc:creator

• Hwang, Taehwan, 1992-

Advisor dc:contributor.advisor

• Wood, John L. (John Louis)

• Total synthesis.
• Natural products.
• Diterpenoids.
• Diketopiperazines.
• Diels-Alder cycloaddition.

Statement dc:rights

• Baylor University works are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. Contact libraryquestions@baylor.edu for inquiries about permission.

Language dc:language.iso

en

Handle dc:identifier.uri

https://hdl.handle.net/2104/12772

OAI identifier oai:identifier

oai:baylor-ir.tdl.org:2104/12772