Studies towards the total synthesis of n-methylwelwitindolinone C isothiocyanate

Vivant, Bick (2012). Studies towards the total synthesis of n-methylwelwitindolinone C isothiocyanate. University of Birmingham. Ph.D.

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Abstract

N-Methylwelwitindolinone C isothiocyanate (7), isolated from the blue green algae Hapalosiphon welwitschii and Westiella intricate, is a structurally novel alkaloid related to the welwitindolinone family. This thesis describes studies towards the total synthesis of this natural product.
Chapter One introduces the biological activities and the proposed biosyntheses of the welwitindolinone alkaloids. The synthetic studies towards the synthesis of this class of natural products will be also discussed.
Chapter Two describes the different strategies towards the synthesis of a bicyclo[4.3.1]decane scaffold possessing a gem-dimethyl group present in the natural product 7. The geminal group was envisioned via a methyl addition to a carbonyl, a deprotonation of a sulfone or an intramolecular Michael addition. Generation of the desired skeleton 182 was achieved by using an intramolecular palladium-catalysed α-arylation of a trimethylsilyl enol ether.
Chapter Three describes various attempts to the direct installation of a nitrogen functionality at the bridgehead position. In an indirect mode, a regioselective deprotonation allowed functionalisation of the desired bridgehead position and the access to isocyanate 297 and diketoazide 276, respectively obtained from a [3,3]-sigmatropic rearrangement and an aza- Michael reaction. A three step sequence involving a regioselective deprotonation of diketoazide 276, followed by aldol condensation and dehydration led to the advance intermediate 306.
Chapter Four describes the recent breakthrough in the synthesis of the welwitindolinone alkaloids. The total synthesis of N-methylwelwitindolinone D isonitrile (19) and N-methylwelwitindolinone C isothiocyanate (7), along with related studies reported this year.
Chapter Five includes the experimental procedures and analytical data for the preparation of novel compounds described during the course of this study.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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