Title: Crystallization in drug discovery and development: stories from process and medicinal chemistry

Abstract: Crystallization plays distinct, high‑value roles across the drug discovery and development continuum - from a decisive compass for structure‑guided medicinal chemistry to an enabling workhorse of process chemistry. This dual utility will be illustrated through two case studies. First, an industrial synthesis of an antimalarial clinical candidate showcases a fully crystallization‑based route eliminating all chromatographic purifications. Strategic discovery of multiple crystalline intermediates spanning a diastereoselective Claisen rearrangement/salt resolution, stereoselective iodolactonization, and stepwise formation of a densely substituted diazabicyclo[6.2.0]decane system enabled clinical entry of an antimalarial with a novel mechanism-of-action. Second, in a medicinal chemistry setting targeting an immune receptor, iterative X‑ray co‑crystallography transformed a historically shallow, “undruggable” sialic acid binding site into a ligandable pocket and led to discovery of ligands with nanomolar affinity.