Starting out - Treating a patient with pressure ulcers has taught me compassion.

While on an acute placement at the end of my second year of training, I helped to look after a patient who was admitted to hospital from her home following gradual deterioration of health and reduced mobility.

Asymmetric hydrogenation of protected allylic amines.

A general method for the enantioselective hydrogenation of protected allylic amine derivatives is described. This procedure relies on the generation of a cationic ruthenium complex with the axially chiral ligand (-)-TMBTP. The utility is highlighted by the highly enantioselective hydrogenation of a diene substrate that can then be elaborated to prepare Telcagepant, a compound currently in Phase III clinical trials. The scope of the hydrogenation reaction was studied, and a variety of substituted allylic amine derivatives could be hydrogenated with enantiomeric ratios of 92:8 or higher.

Antisense-guided isolation and structure elucidation of pannomycin, a substituted cis-decalin from Geomyces pannorum.

Antisense-based screening strategies can be used to sensitize a microorganism and selectively detect inhibitors against a particular cellular target of interest. A strain of Staphylococcus aureus that generates an antisense RNA against SecA,a central member of the protein secretion machinery, has been used to screen for novel antibacterials. Possible inhibitors of the SecA ATP-ase were selected with a high-throughput, two-plate agar-based whole cell differential sensitivity screen. After screening a library of over 115 000 natural products extracts with the SecA antisense strain, an extract of Geomyces pannorum was identified as providing increased activity against the sensitized strain as compared with the wild-type control. Bioassay-guided isolation of the active component from this fungal extract provided a new cis-decalin secondary metabolite, which we have named pannomycin.

Raney-Co mediated reductive cyclization of an alpha,beta-unsaturated nitrile.

An expedient, five step synthesis of caprolactam 1 is reported starting from natural L-homoserine. The key step is a chemoselective reductive cyclization of alpha,beta-unsaturated nitrile 10 mediated by Raney-Co type metals. This hydrogenation is extensively investigated in order to account for the observed product distribution and yields.

Enol tosylates as viable partners in Pd-catalyzed cross-coupling reactions.

[reaction: see text] Herein we demonstrate functionalized enol tosylates to be robust substrates that undergo Suzuki-Miyaura, Sonogashira, and Stille cross-coupling reactions to provide stereodefined trisubstituted unsaturated esters.

Stereoselective enol tosylation: preparation of trisubstituted alpha,beta-unsaturated esters.

[Reaction: see text] The stereoselective preparation of (E)- or (Z)-trisubstituted alpha,beta-unsaturated esters in three steps from N-protected glycine is presented. The key step in the synthesis is the highly selective enol tosylation of gamma-amino beta-keto esters. The enol tosylates are stable, crystalline compounds that undergo smooth and effective Suzuki-Miyaura coupling reaction with a variety of aryl boronic acids.

A new ene-triyne antibiotic from the fungus Baeospora myosura.

The isolation and structure elucidation of 1 from the Basidomycete fungus Baeospora myosura is described. This new ene-triyne antibiotic was most potent against Gram-positive bacteria, while it was less active against Gram-negative bacteria and a yeast. MICs against several strains of Staphylococcus aureus were as low as 0.001 microg/mL. Analogues of 1 that did not contain the ene-triyne moiety were inactive against all microorganisms tested. The isolation of this new natural product was complicated by the highly reactive nature of the conjugated terminal polyacetylene.