Christopher J. Chapman

Efficient aromatic and heteroatom acylations using catalytic indium complexes with lithium perchlorate

The combination of an indium complex with lithium perchlorate affords a potent system for the catalytic acylation of electron-rich aromatics and alcohols. The use of isopropenyl acetate as acyl donor results in cleaner methodology with acetone as the only by-product. The study has also revealed an indium-catalysed ketalisation reaction.

Rhodium catalysed tandem conjugate addition-protonation: an enantioselective synthesis of 2-substituted succinic estersElectronic supplementary information (ESI) available: experimental procedures and HPLC data. See http://www.rsc.org/suppdata/cc/b4/b406905f/

The rhodium catalysed addition of potassium trifluoro(organo)borates to dimethyl itaconate generates an intermediate complex which on protonation provides enantioenriched succinic esters.

Enantioselective rhodium-catalysed addition of boronic acids using C2-symmetric aryl diphosphite ligands

The enantioselective rhodium-catalysed conjugate addition of aryl boronic acids to dehydroalanine derivatives has been successfully carried out in the presence of C2-symmetric aryl diphosphite ligand (R,R,R-4) to prepare unnatural amino acid esters. The products have been obtained in up to 72% ee and with good isolated yield.

Diphosphine mono-sulfides: readily available chiral monophosphines

Enantiomerically pure (R)-BINAP, (R)-Tol-BINAP, (R,R)-Me-DUPHOS and (R,R)-DIOP were converted into the corresponding mono-sulfides by treatment with elemental sulfur in benzene.

Site-selective modification of peptides using rhodium and palladium catalysis: complementary electrophilic and nucleophilic arylation

The site-selective modification of peptides containing dehydroalanine, tyrosine and tryptophan residues has been achieved using rhodium catalysed conjugate additions or palladium catalysed aryl-amination and -etherification reactions.

Optimisation of tetrahydroisoquinoline-based chimeric microtubule disruptors.

Tetrahydroisoquinoline (THIQ)‐based “chimeric” microtubule disruptors were optimised through modification of the N‐benzyl motif, in concert with changes at C3 and C7, resulting in the identification of compounds with improved in vitro antiproliferative activities (e.g. 15: GI50 20 nM in DU‐145). The broad anticancer activity of these novel structures was confirmed in the NCI 60‐cell line assay, with 12 e,f displaying MGM values in the 40 nM region. In addition, their profiles as inhibitors of tubulin polymerisation and colchicine binding to tubulin were confirmed. Compound 15, for example, inhibited tubulin polymerisation with an IC50 of 1.8 μM, close to that of the clinical drug combretastatin A‐4, and also proved effective at blocking colchicine binding. Additionally, compound 20 b was identified as the only phenol in the series to date showing both better in vitro antiproliferative properties than its corresponding sulfamate and excellent antitubulin data (IC50=1.6 μM). Compound 12 f was selected for in vivo evaluation at the NCI in the hollow fibre assay and showed very good activity and wide tissue distribution, illustrating the value of this template for further development.