17 research outputs found
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)Âmethanol
(<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 palladiumÂ(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