Chemoenzymatic Total Syntheses of Some Biologically Relevant Scaffolds in Homochiral Form
Creators: name: Yang, Shuxin
Publisher: name: The Australian National University
Year: 2017
Subjects: cis-1,2-Dihydrocatechols
Chemoenzymatic total synthesis
Natural product
Bioactivity
Enantiomerically pure

description: Since time immemorial certain plants and/or extracts thereof have been used for the treatment of various diseases. The utility of such materials is normally attributed to the specific chemical components within the source plants. For this reason, chemists have sought to isolate the active principals for evaluation and the more efficacious ones have been the subject of synthetic studies. Since biological activity is normally embodied in one but not the other enantiomeric form of homochiral natural products, the selective synthesis of such species has become an important aspect of such endeavours. The use of chirons for such purposes has often provided a very effective means of obtaining a given enantiomeric form of the target compound. Since various enantiomerically pure cis-1,2-dihydrocatechols (such as compounds 3c and 3d) have become available in large quantity via the whole-cell biotransformation of certain halogenated arenes they have become particularly important starting materials in natural product synthesis. This is all the more so with the recognition that the “hidden symmetry elements” embodied within such chirons can allow for the generation of either enantiomeric form of a target compound from a single enantiomeric form of such starting materials, a process sometimes termed enantiodivergent synthesis. In this thesis, approaches to the syntheses of the biologically significant systems such as ent-kirkamide, (+)-lycorine, and (+)-narseronine are described by using enzymatically generated cis-1,2-dihydrocatechols.Specifically, the first chapter of this thesis analyses the current state-of-play with respect to the generation of cis-1,2-dihydrocatechols of the general form 3 and their application in chemical synthesis, especially as this applies to the assembly of biologically active natural products and related systems. The approaches employed in establishing a near-to-complete total synthesis of ent-kirkamide from (1S,2S)-3-bromocyclohexa-3,5-diene-1,2-diol (3c) and its iodo-counterpart 3d are described in Chapter Two. This is preceded by a commentary on the origins, structural elucidation and biological properties of the natural product (viz. kirkamide) along with a description of the only total synthesis of this compound reported to date. A chemoenzymatic approach to the total synthesis of (+)-lycorine using (1S,2S)-3-bromocyclohexa-3,5-diene-1,2-diol (3c) as starting material is discussed in the third chapter. This is preceded by a description of the synthetic approaches (reported by others) to either the (+)- or (–)-form of lycorine. The work reported in the fourth chapter on the successful synthesis of (+)-narseronine from the bromobenzene-derived metabolite 3c serves to emphasize the utility of cis-1,2-dihydrocatechols as chiral building blocks. Since earlier work within the Banwell Group had resulted in the development of a synthesis of (–)-narseronine from the same starting material, the present work serves to emphasize the capacity for undertaking enantiodivergent syntheses using the “pseudo-symmetric” cis-1,2-dihydrocatechol 3c as starting material.