Flexible synthesis of spirocyclic pyrans and piperidines

Ferrari, Frank D. (2012) Flexible synthesis of spirocyclic pyrans and piperidines. PhD thesis, University of Glasgow.

Abstract

Spirocyclic piperidines and spirocyclic pyrans are prevalent throughout nature, often appearing in natural products which exhibit exciting biological activities. Notable examples of spirocyclic piperidine-containing biologically active natural products are halichlorine, pinnaic acid and tauropinnaic acid.
Despite their structural similarity, halichlorine and the pinnaic acids were isolated from separate organisms; halichlorine was isolated from extracts of the marine sponge Halichondria okadai while both pinnaic acid and tauropinnaic acid were isolated from the Okinawan bivalve mollusc Pinna muricata.
The complex hybrid molecule polymaxenolide contains a representative spirocyclic pyran core. The biological profile of polymaxenolide is not yet known, however its hybrid origins have rendered it a target of significant interest.
The work described herein details the development of a methodology capable of accessing both spirocyclic pyran and spirocyclic piperidine core structures from a common cyclic tertiary furfuryl alcohol intermediate. The key spirocycle forming step involves the oxidative rearrangement of cyclic tertiary furfuryl alcohols and amines for the synthesis of spirocyclic pyrans and piperidines, respectively.
Efforts towards the synthesis of a complex, africanane-derived Southern fragment, with the intention of applying this methodology towards the synthesis of polymaxenolide are reported.
This methodology has been further elaborated to complete an asymmetric synthesis of the upper framework of an oxa-analogue of pinnaic acid.
The potential for a spectator protecting group free synthesis of pinnaic acid was also explored and the synthesis of an advanced intermediate is also reported.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Spirocycle formation, Pyrans, Piperidines, Natural product synthesis, Achmatowicz oxidative rearrangement
• Subjects: Q Science > QD Chemistry
• Colleges/Schools: College of Science and Engineering > School of Chemistry
• Supervisor's Name: Marquez, Dr. Rodolfo
• Date of Award: 2012
• Depositing User: Mr Frank D Ferrari
• Unique ID: glathesis:2012-3829
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 04 Jan 2013 11:39
• Last Modified: 04 Jan 2013 11:41
• URI: https://theses.gla.ac.uk/id/eprint/3829