The combination of three reagents—a tridentate pybox ligand (pybox=pyridine bis(oxazoline)), magnesium perchlorate, and Hünig base (iPr2EtN)—allows the catalytic generation of a chiral glycine enolate from 1 that undergoes highly enantioselective addition to a range of aryl aldehydes 2. The protected aryl β‐hydroxy‐α‐amino acid products obtained include a protected version of one of the aryl serine units present in the glycopeptide antibiotic vancomycin.

A catalyst generated from Pd(dba)2 and the bulky electron-rich phosphine ligand 2-(dicyclohexylphosphino)-2',4', 6'-tri-i-propyl-1-1'-biphenyl is effective for the alpha-arylation of oxindoles. Generation of the potassium-enolates of a range of oxindoles allows coupling with aryl chlorides, bromides, and triflates. Significant variation of the substitution pattern on both the oxindole and aryl halide is possible.

The PIM family of serine/threonine kinases have become an attractive target for anti-cancer drug development, particularly for certain hematological malignancies. Here, we describe the discovery of a series of inhibitors of the PIM kinase family using a high throughput screening strategy. Through a combination of molecular modeling and optimization studies, the intrinsic potencies and molecular properties of this series of compounds was significantly improved. An excellent pan-PIM isoform inhibition profile was observed across the series, while optimized examples show good selectivity over other kinases. Two PIM-expressing leukemic cancer cell lines, MV4-11 and K562, were employed to evaluate the in vitro anti-proliferative effects of selected inhibitors. Encouraging activities were observed for many examples, with the best example (44) giving an IC of 0.75μM against the K562 cell line. These data provide a promising starting point for further development of this series as a new cancer therapy through PIM kinase inhibition.

Two palladium-catalysed amination protocols are deployed in the desymmetrisation of the complex dimeric alkaloid meso-chimonanthine. The power of these transformations is showcased in an efficient formal and total synthesis of the natural products hodgkinsine and hodgkinsine B, respectively.

Aller guten Dinge sind drei Reagentien: Ein katalytisches System aus einem dreizähnigen Pybox‐Liganden (Pybox=Bis(oxazolinyl)pyridin), Magnesiumperchlorat und der Hünig‐Base (iPr2EtN) erzeugt das chirale Glycinenolat von 1, das hoch enantioselektiv an Arencarbaldehyde 2 addiert. Unter den so erhältlichen geschützten Aryl‐β‐hydroxy‐α‐aminosäuren ist auch eine geschützte Version einer der Arylserin‐Einheiten des antibiotischen Glycopeptids Vancomycin.

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As part of a long-term goal directed towards the ab initio asymmetric synthesis of unnatural amino sugars, the doubly diastereoselective conjugate addition reactions of the antipodes of lithium N-benzyl-N-(alpha-methylbenzyl)amide to a range of homochiral alpha,beta-unsaturated esters containing cis- and trans-dioxolane units was investigated. These reactions resulted in "matching" and "mismatching" effects. In the "matched" cases a single diastereoisomer of the corresponding beta-amino ester (containing three contiguous stereocentres) is produced. Upon conjugate addition to a homochiral alpha,beta-unsaturated ester containing a cis-dioxolane unit, in the "mismatched" case it is the stereocontrol of the substrate which is dominant over that of the lithium amide, whilst upon addition to homochiral alpha,beta-unsaturated esters containing a trans-dioxolane unit the stereocontrol of the homochiral lithium amide is dominant. Hydrogenolytic N-deprotection of the beta-amino ester products of conjugate addition gives access to polyoxygenated beta-amino acid derivatives.

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