Towards the total synthesis of the asbestinins

Mat Som, Ian Shah Reen (2016) Towards the total synthesis of the asbestinins. PhD thesis, University of Glasgow.

Abstract

The asbestinins were isolated as the principal diterpenes from extracts of Briareum asbestinum collected by Faulkner and co-workers in 1980. The carbon skeleton of the asbestinins is related to that of cladiellins and briarellins by migration of a methyl group from C11 to C12. To date, the asbestinins represent the most evolved subclass of 2,11-cyclised cembranoid family of natural products, featuring a tetracyclic ring system with nine contiguous stereocenters and a polycyclic fully-substituted tetrahydrofuran. Several of the asbestinin natural products demonstrate diverse bioactivities such as cytotoxicity against tumour cells, antimicrobial activity and antagonism to both histamine and acetylcholine. These compounds are particularly interesting due to their complex structures and broad range of biological activities. This thesis describes the attempted total synthesis of (±)-11-acetoxy-4-deoxyasbestinin D.

Initially, large-scale preparation of the tricyclic core of the asbestinins was achieved using a samarium diiodide reductive cyclisation reaction to generate tetrahydropyranol motif, [2,3]-sigmatropic rearrangement of an oxonium ylide generated from a functionalised diazoketone and an intermolecular Diels-Alder cycloaddition reaction.

The work set forth in the second part deals with the challenges encountered during installation a C12 methyl group of the asbestinins in a stereoselective manner. The final part concerns successful efforts directed towards the synthesis of the complete tetracyclic core of the asbestinins.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: asbestinins, total synthesis, natural product.
• Subjects: Q Science > QD Chemistry
• Colleges/Schools: College of Science and Engineering > School of Chemistry
• Supervisor's Name: Clark, Professor J. Stephen
• Date of Award: 2016
• Embargo Date: 6 January 2020
• Depositing User: Ian Shah Reen Mat Som
• Unique ID: glathesis:2016-7852
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 03 Feb 2017 11:37
• Last Modified: 03 Mar 2017 08:59
• URI: https://theses.gla.ac.uk/id/eprint/7852