Synthesis of ((3<i>R</i>,6<i>R</i>)‑6-Methylpiperidin-3-yl)methanol via Biocatalytic Transamination and Crystallization-Induced Dynamic Resolution

An asymmetric synthesis of orexin receptor antagonist MK-6096 piperidine core, ((3<i>R</i>,6<i>R</i>)-6-methylpiperidin-3-yl)­methanol (<b>3</b>), is described. The target is synthesized in four steps and 40% overall yield from methyl vinyl ketone and diethyl malonate. The key operation is a practical crystallization-induced dynamic resolution for the conversion of a trans/cis mixture of lactam acid <b>17</b> into the desired trans-lactam acid salt in >95% de and 91% yield. The substrate lactam acid mixture was prepared via a solvent-free Michael reaction and a practical biocatalytic transamination process

Synthesis of Antifungal Glucan Synthase Inhibitors from Enfumafungin

An efficient, new, and scalable semisynthesis of glucan synthase inhibitors <b>1</b> and <b>2</b> from the fermentation product enfumafungin <b>3</b> is described. The highlights of the synthesis include a high-yielding ether bond-forming reaction between a bulky sulfamidate <b>17</b> and alcohol <b>4</b> and a remarkably chemoselective, improved palladium­(II)-mediated Corey-Yu allylic oxidation at the highly congested C-12 position of the enfumafungin core. Multi-hundred gram quantities of the target drug candidates <b>1</b> and <b>2</b> were prepared, in 12 linear steps with 25% isolated yield and 13 linear steps with 22% isolated yield, respectively