Synthetic Studies Towards Mescengricin
type: CreativeWork
description: This thesis describes the synthetic efforts towards mescengricin (80), an ɑ-carboline alkaloid isolated from a culture of Streptomyces griseoflavus. Mescengricin (80) may be a prominent neuroprotectant for ischemic injury as it protected chick primary mesencephalic neurons from L-glutamate toxicity with an EC50 of 6.0 nM. A model study was conducted to obtain the oxazoloindole to attempt the intermolecular aza- Diels-Alder reaction. Treatment of 250 to the Robinson-Gabriel cyclodehydration gratifyingly afforded 259. Though in low yield, the desired ɑ-carboline scaffold 287 was afforded after heating 259 with methyl acrylate. Deprotection of the indole nitrogen to 288 was thought to favour this aza-Diels-Alder reaction, however, 289 was produced. Establishing a route to construct the ɑ-carboline scaffold led us to pursue the same route with 298. Treatment of 298 to the Robinson-Gabriel cyclodehydration gave 291 in meagre yield. Nevertheless, the aza- Diels-Alder reaction between 291 and methyl acrylate was attempted, however, this led to complex mixtures. Deacetylation of 291 afforded 300, however, this also led to complex mixtures upon attempted aza-Diels-Alder reaction with methyl acrylate. Due to the unsuccessful synthesis of the desired methoxy ɑ-carboline, an alternative strategy was sought. We envisaged that treating 324 to formic acid for the second generation route would give 325, which would afford 323 upon cyclisation. Unfortunately, subjecting 329 to the coupling-intramolecular cyclisation pathway with 2-cyanoacetic acid (330) formed a complex mixture. We then attempted to repeat this reaction using ethyl 2-cyanoacetate (333) to form 334. With 334 in hand, it was subjected to formic acid, hoping that 336 would form and then cyclise in situ to generate 323. Unfortunately, the reaction stalled at 336 and gradually degraded upon increasing the reaction time. Next, 336 was subjected to acidic and basic conditions, however, this led to the reformation of 334 an…
abstract: This thesis describes the synthetic efforts towards mescengricin (80), an ɑ-carboline alkaloid isolated from a culture of Streptomyces griseoflavus. Mescengricin (80) may be a prominent neuroprotectant for ischemic injury as it protected chick primary mesencephalic neurons from L-glutamate toxicity with an EC50 of 6.0 nM. A model study was conducted to obtain the oxazoloindole to attempt the intermolecular aza- Diels-Alder reaction. Treatment of 250 to the Robinson-Gabriel cyclodehydration gratifyingly afforded 259. Though in low yield, the desired ɑ-carboline scaffold 287 was afforded after heating 259 with methyl acrylate. Deprotection of the indole nitrogen to 288 was thought to favour this aza-Diels-Alder reaction, however, 289 was produced. Establishing a route to construct the ɑ-carboline scaffold led us to pursue the same route with 298. Treatment of 298 to the Robinson-Gabriel cyclodehydration gave 291 in meagre yield. Nevertheless, the aza- Diels-Alder reaction between 291 and methyl acrylate was attempted, however, this led to complex mixtures. Deacetylation of 291 afforded 300, however, this also led to complex mixtures upon attempted aza-Diels-Alder reaction with methyl acrylate. Due to the unsuccessful synthesis of the desired methoxy ɑ-carboline, an alternative strategy was sought. We envisaged that treating 324 to formic acid for the second generation route would give 325, which would afford 323 upon cyclisation. Unfortunately, subjecting 329 to the coupling-intramolecular cyclisation pathway with 2-cyanoacetic acid (330) formed a complex mixture. We then attempted to repeat this reaction using ethyl 2-cyanoacetate (333) to form 334. With 334 in hand, it was subjected to formic acid, hoping that 336 would form and then cyclise in situ to generate 323. Unfortunately, the reaction stalled at 336 and gradually degraded upon increasing the reaction time. Next, 336 was subjected to acidic and basic conditions, however, this led to the reformation of 334 an…
author: Ichikawa, Karen
license: https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm
date published: 2023
date modified: 2026-07-24T01:04:34Z
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/2292/68432