Synthetic Studies Towards the Gombaspiroketals and a Cobalt-Catalysed Epoxide Olefination
type: CreativeWork
description: The gombaspiroketals (14-16) are 6,6-spiroketal-containing natural products, which were isolated from a South Korean marine sponge (Clathria gombawuiensis) in 2014. The gombaspiroketals belong to a family of sesterterpenoids derived from the alotane skeleton, some of which exhibit potent and varied bioactivities. Recent total syntheses of alotane natural products has demonstrated the importance of total synthesis efforts in furthering the field of organic chemistry, and for investigating structure-activity relationships and biological properties. Therefore the gombaspiroketals were chosen as a target for synthetic studies. Epoxide 171 was identified as a possible intermediate towards the gombaspiroketals, which was envisioned to be accessed by Hosomi-Sakurai allylation of allylsilane 45 and cyclic acetal 172 followed by epoxidation. This work describes efforts in the syntheses of allylsilane 45 and cyclic acetal 172. Towards allylsilane 45, the literature cuprate conjugate addition of bromide 54 with acrylate 55 was irreproducible, affording ester 56 in varying yields of 0-66%. Alternative transformations were investigated for access to ester 56, including addition of organometallic nucleophiles and transition metal catalysis. Although no method was found to provide reliable access to 56 in consistently good yield, the cobalt- and nickel-catalysed conjugate additions emerged as potential alternatives worthy of further investigation. Subsequent elaboration to allylsilane 45 via intramolecular Horner-Wadsworth-Emmons reaction of 58 proceeded smoothly. Synthesis of aldehyde 303 en route to acetal 172 was investigated. The literature sequence reported from 2-methylcyclohexanone (299) was ineffective, due to presence of inseparable impurities in the final products. 303 was obtained in excellent purity by intramolecular Horner-Wadsworth-Emmons reaction of phosphonate 345 which was reliably accessed on large scale. Aldehyde 303 was unified with phosphonium 358 (derived fro…
abstract: The gombaspiroketals (14-16) are 6,6-spiroketal-containing natural products, which were isolated from a South Korean marine sponge (Clathria gombawuiensis) in 2014. The gombaspiroketals belong to a family of sesterterpenoids derived from the alotane skeleton, some of which exhibit potent and varied bioactivities. Recent total syntheses of alotane natural products has demonstrated the importance of total synthesis efforts in furthering the field of organic chemistry, and for investigating structure-activity relationships and biological properties. Therefore the gombaspiroketals were chosen as a target for synthetic studies. Epoxide 171 was identified as a possible intermediate towards the gombaspiroketals, which was envisioned to be accessed by Hosomi-Sakurai allylation of allylsilane 45 and cyclic acetal 172 followed by epoxidation. This work describes efforts in the syntheses of allylsilane 45 and cyclic acetal 172. Towards allylsilane 45, the literature cuprate conjugate addition of bromide 54 with acrylate 55 was irreproducible, affording ester 56 in varying yields of 0-66%. Alternative transformations were investigated for access to ester 56, including addition of organometallic nucleophiles and transition metal catalysis. Although no method was found to provide reliable access to 56 in consistently good yield, the cobalt- and nickel-catalysed conjugate additions emerged as potential alternatives worthy of further investigation. Subsequent elaboration to allylsilane 45 via intramolecular Horner-Wadsworth-Emmons reaction of 58 proceeded smoothly. Synthesis of aldehyde 303 en route to acetal 172 was investigated. The literature sequence reported from 2-methylcyclohexanone (299) was ineffective, due to presence of inseparable impurities in the final products. 303 was obtained in excellent purity by intramolecular Horner-Wadsworth-Emmons reaction of phosphonate 345 which was reliably accessed on large scale. Aldehyde 303 was unified with phosphonium 358 (derived fro…
author: Quach, ML
license: https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm
date published: 2019
date modified: 2026-07-24T01:04:52Z
provider: University of Auckland
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: ResearchSpace@Auckland

PropertyValue
property ID: Handle
value: https://hdl.handle.net/2292/47516