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dc.contributor.authorWilkie, Ross Philip
dc.contributor.authorNeal, Andrew
dc.contributor.authorJohnston, Craig Andrew
dc.contributor.authorVoûte, Nicholas
dc.contributor.authorLancefield, Christopher Stuart
dc.contributor.authorStell, Matthew
dc.contributor.authorMedda, Federico
dc.contributor.authorMakiyi, Edward Frank
dc.contributor.authorTurner, Emma
dc.contributor.authorOjo, Oluwarotimi Stephen
dc.contributor.authorSlawin, Alexandra Martha Zoya
dc.contributor.authorLebl, Tomas
dc.contributor.authorMullen, Peter
dc.contributor.authorHarrison, David James
dc.contributor.authorIreland, Chris M
dc.contributor.authorWestwood, Nicholas James
dc.identifier.citationWilkie , R P , Neal , A , Johnston , C A , Voûte , N , Lancefield , C S , Stell , M , Medda , F , Makiyi , E F , Turner , E , Ojo , O S , Slawin , A M Z , Lebl , T , Mullen , P , Harrison , D J , Ireland , C M & Westwood , N J 2016 , ' Total synthesis of dehaloperophoramidine using a highly diastereoselective Hosomi-Sakurai reaction ' , Chemical Communications , vol. 52 , no. 71 , pp. 10747-10750 .
dc.identifier.otherORCID: /0000-0002-0269-3221/work/48131737
dc.identifier.otherORCID: /0000-0003-0630-0138/work/56424154
dc.identifier.otherORCID: /0000-0002-9527-6418/work/56861554
dc.identifier.otherORCID: /0000-0001-9041-9988/work/64034227
dc.identifier.otherORCID: /0000-0002-0841-609X/work/157141032
dc.descriptionThe authors would like to acknowledge EPSRC for PhD funding through the Doctoral Training Schemes.en
dc.description.abstractThe 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.
dc.relation.ispartofChemical Communicationsen
dc.subjectQD Chemistryen
dc.subjectSDG 14 - Life Below Wateren
dc.titleTotal synthesis of dehaloperophoramidine using a highly diastereoselective Hosomi-Sakurai reactionen
dc.typeJournal articleen
dc.contributor.institutionUniversity of St Andrews. School of Chemistryen
dc.contributor.institutionUniversity of St Andrews. EaSTCHEMen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.description.statusPeer revieweden

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