Expeditious access to cis-β-aryl, γ-alkyl disubstituted (±)-γ-butyrolactones via nickel-hydride catalysis

The 1,4-reduction of β- and γ-substituted butenolides using 5 mol% of NiCl₂·6H₂O and NaBH₄ in MeOH for rapid access to cis-β,γ-disubstituted γ-butyrolactones is described. The reaction was selective for cis-products, which were obtained in good to excellent yields. This study showcased the influence of steric hindrance and angle strain on the diastereoselectivity outcome of conjugate reductions facilitated by in situ generated nickel-hydride

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

This work was supported by EPSRC Ph.D. studentships (EP/1518175 (DMB), EP/1517938 (AN)), the Industrial Biotechnology Innovation Centre (Ph.D. studentship to DMB), CRITICAT Centre for Doctoral Training (Ph.D. studentship to IP; EP/L016419/1), EPSRC grants EP/J018139/1 and EP/K00445X/1 (SOJO) and an EPSRC Doctoral Prize Fellowship (CSL).Understanding the structure of technical lignins resulting from acid-catalysed treatment of lignocellulosic biomass is important for their future applications. Here we report an investigation into the fate of lignin under acidic aqueous organosolv conditions. In particular we examine in detail the formation and reactivity of non-native Hibbert ketone structures found in isolated organosolv lignins from both Douglas fir and beech woods. Through the use of model compounds combined with HSQC, HMBC and HSQC-TOCSY NMR experiments we demonstrate that, depending on the lignin source, both S and G lignin-bound Hibbert ketone units can be present. We also show that these units can serve as a source of novel mono-aromatic compounds following an additional lignin depolymerisation reaction.PostprintPeer reviewe

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

The authors would like to acknowledge EPSRC for PhD funding through the Doctoral Training Schemes.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.Publisher PDFPeer reviewe

Isothiourea-Catalysed Acylative Kinetic Resolution of Aryl-Alkenyl (sp2 vs sp2) Substituted Secondary Alcohols

aryl-alkenyl (sp2 vs sp2) substituted secondary alcohols is described, with effective enantiodiscrimination achieved using the isothiourea organocatalyst HyperBTM (1 mol%) and isobutyric anhydride. The kinetic resolution of a wide range of aryl-alkenyl substituted alcohols has been evaluated, with either electron-rich or naphthyl aryl substituents in combination with an unsubstituted vinyl substituent providing the highest selectivity (S = 2-1980). The demonstration of this protocol for the gram-scale (2.5 g) kinetic resolution of a model aryl-vinyl (sp2 vs sp2) substituted secondary alcohol is demonstrated, giving access to >1 g of each of the product enantiomers both in 99:1 er

Data underpinning - The synthesis and analysis of lignin-bound Hibbert ketone structures in technical lignins

CCDC 1500178 CCDC 150017

Synthesis of the Natural Product Descurainolide and Cyclic Peptides from Lignin-derived Aromatics (dataset)

CCDC 1505597 (anti-(±)-3), CCDC 1505596 ((S)-2a), CCDC 1505598 ((S)-14b), CCDC 1510492 (anti-(2R, 3R)-3) and CCDC 1506889 ((±)-41) contain the supplementary crystallographic dat

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

CCDC 1486344 CCDC 1478152-147815