Towards the total synthesis of Chrysophaentin F

Abstract

This thesis describes the synthetic work towards the natural product Chrysophaentin F which has been extracted from the alga Chrysophaeum taylori. This bisdiarylbutene macrocycle exhibits antimicrobial properties against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF) (MIC50 (MRSA) = 4.2 ± 1.3 ?g/mL).

Investigation of the key steps on an unchlorinated analogue allowed us to determine what strategy would be best to access the natural product. The formation of the desired core structure relied on a Chan-Lam-Evans coupling reaction, a Pd catalysed coupling reaction and a RCAM reaction to create the pivotal bonds of the complex scaffold. The investigation on a model system to form the vinyl chloride bridge has also been performed bringing insight on the possible regioselectivity of the necessary late stage hydrochlorination reaction.

Finally the synthesis towards the chlorinated macrocycle was started and advanced enough to access some key intermediates which despite some unforeseen difficulties proved that the natural product is now at reach following the strategy developed for the unchlorinated analogue.

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Identifiers

ORCID for David C. Harrowven: orcid.org/0000-0001-6730-3573

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