The cyclo‐dipeptide substrates of the essential M. tuberculosis (Mtb) enzyme CYP121 were deconstructed into their component fragments and screened against the enzyme. A number of hits were identified, one of which exhibited an unexpected inhibitor‐like binding mode. The inhibitory pharmacophore was elucidated, and fragment binding affinity was rapidly improved by synthetic elaboration guided by the structures of CYP121 substrates. The resulting inhibitors have low micromolar affinity, good predicted physicochemical properties and selectivity for CYP121 over other Mtb P450s. Spectroscopic characterisation of the inhibitors′ binding mode provides insight into the effect of weak nitrogen‐donor ligands on the P450 heme, an improved understanding of factors governing CYP121–ligand recognition and speculation into the biological role of the enzyme for Mtb.

The use of Rh catalysts derived from a phospholanephosphite ligand were found to be more productive than the classic rhodium/BINAP system in enantioselective conjugate additions. These catalysts enable the use of lower amounts of aryl boronic acid in an asymmetric arylation reaction that required [a] Dr. ane-phosphite, L1, known as BOBPHOS, [11] gives enhanced reactivity relative to the use of BINAP as the ligand and enabled the preparation of some of the compounds that couldn't be easily be made following standard Rh/BINAP promoted protocols.

A Rh catalyst derived from tri-(2-furyl)phosphine enables the direct reductive amination of 1,3-substituted ketones to occur in high yield and diastereoselectivity.

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