Skip to content

Research at St Andrews

Total synthesis of dehaloperophoramidine using a highly diastereoselective Hosomi-Sakurai reaction

Research output: Contribution to journalArticlepeer-review

DOI

Open Access permissions

Open

Author(s)

Ross Philip Wilkie, Andrew Neal, Craig Andrew Johnston, Nicholas Voûte, Christopher Stuart Lancefield, Matthew Stell, Federico Medda, Edward Frank Makiyi, Emma Turner, Oluwarotimi Stephen Ojo, Alexandra Martha Zoya Slawin, Tomas Lebl, Peter Mullen, David James Harrison, Chris M Ireland, Nicholas James Westwood

School/Research organisations

Abstract

The synthesis of dehaloperophoramidine, a non-halogenated derivative of the marine natural product perophoramidine, is reported. The key steps included a [3,3]-Claisen rearrangement and an epoxide opening/allylsilylation (modified Hosomi-Sakurai) reaction to install the contiguous all-carbon quaternary stereocentres with the required relative stereochemistry. The first five steps were carried out on seventy gram scale without the need for chromatography. Resolution of the [3,3]-Claisen product gave samples of the highly enantiomerically-enriched ketones which are flexible starting points for the synthesis of a number of complex ring structures. A regio- and diastereo-selective iodocyclisation was then used to differentiate between two allyl groups enabling the synthesis of the target molecule by two different routes. A detailed comparison of the trifluoroacetic acid salt of the synthetic dehaloperophoramidine with authentic material was carried out including a key doping experiment. Biological testing showed that (±)-dehaloperophoramidine was cytotoxic to HCT116, HT29 and LoVo colorectal carcinoma cells with comparable activity to that reported for the halogenated perophoramidine. This demonstrated for the first time that the halogens are not essential for the biological activity of this alkaloid class.

Close

Details

Original languageEnglish
Pages (from-to)10747-10750
JournalChemical Communications
Volume52
Issue number71
Early online date5 Aug 2016
DOIs
Publication statusPublished - 14 Sep 2016

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Use of bisulfite processing to generate high-β-O-4 content water-soluble lignosulfonates

    Miles-Barrett, D. M., Montgomery, J. R. D., Lancefield, C. S., Cordes, D. B., Slawin, A. M. Z., Lebl, T., Carr, R. & Westwood, N. J., 6 Feb 2017, In: ACS Sustainable Chemistry & Engineering . 5, 2, p. 1831-1839 9 p.

    Research output: Contribution to journalArticlepeer-review

  2. The synthesis and analysis of lignin-bound Hibbert ketone structures in technical lignins

    Miles-Barrett, D., Neal, A., Hand, C., Montgomery, J., Panovic, I., Ojo, O. S., Lancefield, C. S., Cordes, D. B., Slawin, A. M. Z., Lebl, T. & Westwood, N. J., 14 Nov 2016, In: Organic & Biomolecular Chemistry. 14, 42, p. 10023-10030 8 p.

    Research output: Contribution to journalArticlepeer-review

  3. The Synthesis of Melohenine B and a Related Natural Product

    Lancefield, C. S., Zhou, L., Lebl, T., Slawin, A. M. Z. & Westwood, N. J., 21 Dec 2012, In: Organic Letters. 14, 24, p. 6166-6169 4 p.

    Research output: Contribution to journalArticlepeer-review

  4. Polycyclic ethers and an unexpected dearomatisation reaction during studies towards the bioactive alkaloid, perophoramidine

    Johnston, C. A., Wilkie, R. P., Krauss, H., Neal, A. R., Slawin, A. M. Z., Lebl, T. & Westwood, N. J., 28 Jun 2018, In: Tetrahedron. 74, 26, p. 3339-3347

    Research output: Contribution to journalArticlepeer-review

Related by journal

  1. Chemical Communications (Journal)

    Nigel Peter Botting (Editor)

    2005 → …

    Activity: Publication peer-review and editorial work typesEditor of research journal

Related by journal

  1. Direct synthesis of polyureas from the dehydrogenative coupling of diamines and methanol

    Kumar, A., Armstrong, D., Peters, G., Nagala, M. & Shirran, S. L., 21 May 2021, In: Chemical Communications. Advance Articles, 4 p.

    Research output: Contribution to journalArticlepeer-review

  2. Tilting and twisting in a novel perovzalate, K3NaMn(C2O4)3

    He, X., Zhang, X., Ji, B., Yao, W., Lightfoot, P. & Tang, Y., 4 Feb 2021, In: Chemical Communications. 57, 20, p. 2567-2570

    Research output: Contribution to journalArticlepeer-review

  3. Manganese-catalysed transfer hydrogenation of esters

    Oates, C., Widegren, M. B. & Clarke, M., 7 Aug 2020, In: Chemical Communications. 56, 61, p. 8635-8638

    Research output: Contribution to journalArticlepeer-review

  4. Uncovering the chemistry of C-C bond formation in C-nucleoside biosynthesis: crystal structure of a C -glycoside synthase/PRPP complex

    Gao, S., Radadiya, A., Li, W., Liu, H., Zhu, W., De Crécy-Lagard, V., Richards, N. G. J. & Naismith, J. H., 14 Jul 2020, In: Chemical Communications. 56, 55, p. 7617-7620 4 p.

    Research output: Contribution to journalArticlepeer-review

  5. Unprecedented tin iodide perovskite-like structures featuring ordering of organic moieties

    McNulty, J. A. & Lightfoot, P., 28 Apr 2020, In: Chemical Communications. 56, 33, p. 4543-4546

    Research output: Contribution to journalArticlepeer-review

ID: 244841236

Top