Synthesis of the natural product descurainolide and cyclic peptides from lignin-derived aromatics

Stephen Ojo, O. et al. (2018) Synthesis of the natural product descurainolide and cyclic peptides from lignin-derived aromatics. Organic and Biomolecular Chemistry, 16(2), pp. 266-273. (doi: 10.1039/c7ob02697h) (PMID:29242868)

Abstract

Alternative sources of potential feedstock chemicals are of increasing importance as the availability of oil decreases. The biopolymer lignin is viewed as a source of useful mono-aromatic compounds as exemplified by the industrial scale production of vanillin from this biomass. Alternative lignin-derived aromatics are available in pure form but to date examples of the use of these types of compounds are rare. Here we address this issue by reporting the conversion of an aromatic keto-alcohol to the anti- and syn-isomers of Descurainolide A. The key step involves a rhodium-catalyzed allylic substitution reaction. Enantio-enriched allylic alcohols were generated via an isothiourea-catalyzed kinetic resolution enabling access to both the (2R,3R) and (2S,3S) enantiomers of anti-Descurainolide A. In addition we show that the lignin-derived keto-alcohols can be converted into unnatural amino acid derivatives of tyrosine. Finally, these amino acids were incorporated into cyclic peptide scaffolds through the use of both chemical and an enzyme-mediated macrocylisation.

• Item Type: Articles
• Additional Information: We would like to acknowledge the EPSRC UK National Mass Spectrometry Facility at Swansea University for mass spectrometry analysis. Financial support from: the Engineering and Physical Sciences Research Council (grant EP/J018139/1, EP/K00445X/1 (NJW, ADS, OSO), the doctoral training grant (ARN) and the CRITICAT Centre for Doctoral Training [Ph.D. studentship to SFM; Grant code: EP/L016419/1]), the Leverhulme Trust (JET), European Research Council (ERC-2013-ADG (JHN)).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Wilson, Mr Liam
• Authors: Stephen Ojo, O., Nardone, B., Musolino, S. F., Neal, A. R., Wilson, L., Lebl, T., Slawin, A. M. Z., Cordes, D. B., Taylor, J. E., Naismith, J. H., Smith, A. D., and Westwood, N. J.
• College/School: College of Science and Engineering > School of Chemistry
• Journal Name: Organic and Biomolecular Chemistry
• Publisher: Royal Society of Chemistry
• ISSN: 1477-0520
• ISSN (Online): 1477-0539
• Published Online: 01 December 2017