Use this URL to cite or link to this record in EThOS:
Title: Studies towards the total synthesis of the pyrronazols
Author: McLennan, Ross Sinclair
ISNI:       0000 0004 7960 8114
Awarding Body: University of St Andrews
Current Institution: University of St Andrews
Date of Award: 2019
Availability of Full Text:
Access from EThOS:
Full text unavailable from EThOS. Thesis embargoed until 19 Feb 2024
Access from Institution:
In 2014, the pyrronazols, a family of closely related natural products were isolated from a soil dwelling myxobacteria, Nannocystis pusilla strain Ari7. The family represent a novel structural class of secondary metabolites, containing a conjugated chlorinated pyrrole-oxazole unit. The total synthesis of pyrronazols A and A2, 20 and 21, has still to be accomplished and is of specific interest, not only for its unusual and interesting structure, but also to expand on the very limited biological profile. This could be probed further through the synthesis of structural analogues, thus requiring a synthetic strategy that tolerates rapid modifications to probe SAR. A synthetic strategy for the pyrronazol family must be flexible to allow for the synthesis of both isomers from a single privileged intermediate. Through our attempts towards the synthesis of the pyrronazol family this work details a highly syn-selective, substrate controlled vinylogous Mukaiyama aldol reaction (vMAR) which has been developed and optimised to install the required stereocentres on the pyranone ring. The (4S,5S) C₁-C₇ pyranone fragment has been utilised in the synthesis of two advanced intermediates, both a single reduction step away from pyrronazol A2, that have proved resistant to reduction. The alkene geometry, directing the synthesis towards pyrronazol A2, was set by an unprecedently selective Knoevenagel condensation between 5-chloro-2-formylpyrrole and amidoester partners. Our C₁-C₇ fragment has also been used in a convergent, modular synthesis of pyrronazol B, which afforded the natural product alongside an isomeric product.
Supervisor: Florence, Gordon John Sponsor: Leverhulme Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Natural products ; Total synthesis ; QD415.M6 ; Natural products--Synthesis ; Microbial metabolites