The Application of Dioxygenase-Based Chemoenzymatic Processes to the Total Synthesis of Natural Products

Ye, Sebastian

The Application of Dioxygenase-Based Chemoenzymatic Processes to the Total Synthesis of Natural Products

Date

2023

Authors

Ye, Sebastian

Abstract

The ability to control the stereochemical outcomes of chemical reactions is a key issue associated with many synthetic endeavours, especially those involving the assembly of complex organic compounds containing sp3-hybridized carbon centres and wherein a single stereochemical (often enantiomeric) form of the target is required. Several distinct and versatile strategies are available for effecting such conversions, including ones that start with compounds derived from the chiral pool (the chiron approach), ones involving the attachment of a chiral auxiliary and those that employ asymmetric catalysis. Within the vast realm of asymmetric catalysis, enzymes have either been used directly to effect enantioselective conversions or have served as inspirations for the design of new chiral catalysts that enable such outcomes. The publications presented herein serve to further demonstrate the utility of enzymatically produced and abundant cis-1,2-dihydrocatechols as precursors to a diverse range of enantiomerically pure and particularly versatile synthons. Specifically, sequential stereoselective transformations of certain cis-1,2-dihydrocatechols have enabled enantiodivergent access to highly substituted cyclohexadienones that incorporate an all-carbon quarternary centre. Extensions of this methodology have led to formal total syntheses of the alkaloid aspidophytine and its optical antipode. Additionally, a chemoenzymatic synthesis of the decahydro-1H-cyclopenta[c]indene framework encountered in various natural products was achieved by starting with an enzymatically derived cis-1,2-dihydrocatechol. A key step involved in this sequence is the photochemically promoted oxa-di-pi-methane rearrangement of a compound embodying the core of the platencin framework.