Nanomole-scale high-throughput chemistry for the synthesis of complex molecules

TLDR

When chemists synthesize compounds, the threshold for success has been at least a milligram of product for decades, a constraint driven by characterization limitations despite biochemical assays now operating in microgram quantities. The authors aim to develop an automated dosing and characterization protocol to optimize reaction conditions at the microgram scale. They employ an automated dosing and characterization protocol to systematically optimize reaction conditions on the microgram scale. The protocol enabled screening of numerous base and ligand combinations for catalytic C‑N bond‑forming reactions between scarce complex compounds that previously resisted standard coupling conditions. Buitrago Santanilla et al., Science, this issue p.

Abstract

Breaking through the milligram floor When chemists synthesize compounds, the threshold for success is at least a milligram of product. This has been true for decades—even though biochemical assays have long since descended into microgram territory—and results in part from the constraints of characterization methods. Buitrago Santanilla et al. present an automated dosing and characterization protocol for optimizing chemical reaction conditions on the microgram scale. This allowed them to screen numerous base and ligand combinations for catalytic C-N bond-forming reactions between complex pairs of compounds, in short supply, that resisted standard coupling conditions. Science , this issue p. 49