RESEARCH & PRACTICE
Total Synthesis of the Jiadifenin Family of Natural Products
A reaction must do more than work once: it needs to be reproducible and scalable enough to keep supplying downstream research.
From a working reaction to a dependable research supply
In work on jiadifenin and related natural products, we treated route design, small-scale validation, scale-up, and material preparation as dependent parts of a collective synthesis effort. Exploration began at roughly 1 mg scale. Intermediates from the first two steps were gradually scaled to experiments at about 100 g. The question was not only whether a reaction happened, but whether it could be reproduced, scaled, and used to supply the work downstream.
Redesign the route that became the bottleneck
An early route worked on a small scale but did not scale effectively and increasingly held back later research. I redesigned the route and brought the alternative to a workable state. It then entered scale-up and material-preparation work, becoming a foundation for subsequent collective synthesis research.
Keep exploration and material preparation moving together
Within a core group of about five people, with roughly ten undergraduates involved over time, I assigned route exploration, small-scale validation, scale-up, and preparation tasks to suit each member's strengths. I advanced downstream research and upstream supply in parallel, tracking dependencies and reassigning experiments and people when a route or supply step became blocked.
The roughly 100 g scale applies only to intermediates from the route's first two steps. The core group had about five people and about ten undergraduates participated over time; this does not imply a formal line-management role.