Daniel DiRocco

Daniel DiRocco

Vitals

Current affiliation: Merck & Co.

Age: 32

Ph.D. alma mater: Colorado State University

Advice for young scientists: “Try every idea and never talk yourself out of an experiment. Some of the most meaningful discoveries were the product of pure serendipity.”

Role model: Albert Einstein “for his humility in life and in science.”

As a full-time chemist and the father of a two-year-old, Daniel DiRocco doesn’t have much time for hobbies. If he does find a spare hour, he’s likely to spend it in the computer-controlled home brewery he built in his garage. His current goal is to master lager making. “Lager has a little more process chemistry than the ales most home brewers make,” he says.

It’s no surprise that DiRocco would favor a hobby that involves understanding complex systems. As leader of the catalysis group in process chemistry at Merck & Co., it’s his job to figure out the best reactions for making molecules on large scales so enough can be made for clinical trials or even for manufacturing on the metric-ton scale if a candidate compound is approved as a drug. The quick-and-dirty routes used to make compounds during drug discovery are rarely suitable for scaling those same molecules up, DiRocco says. Yields can be low, or the reagents used to make them can be too expensive. “If we have to make a compound on a large scale, we have to make it as quickly, efficiently, and economically as possible. Generally, that means completely redesigning how it was put together.”

Research at a glance

Synthesizing molecules with a chiral phosphorus is tough. But a metal-free, small-molecule catalyst developed by DiRocco’s team makes chiral nucleoside phosphoramidates, such as Merck’s hepatitis C candidate therapy MK-3682. Yang H. Ku/C&EN/Shutterstock

Synthesizing molecules with a chiral phosphorus is tough. But a metal-free, small-molecule catalyst developed by DiRocco’s team makes chiral nucleoside phosphoramidates, such as Merck’s hepatitis C candidate therapy MK-3682.
Yang H. Ku/C&EN/Shutterstock

In particular, DiRocco’s group specializes in bringing modern asymmetric catalysis methods and innovative new reactions to Merck’s manufacturing processes. For example, his team recently discovered a metal-free, small-molecule catalyst for making chiral nucleoside phosphoramidates—a motif that’s becoming popular in drug molecules, such as Merck’s clinical candidate MK-3682 and Gilead’s Sovaldi, both hepatitis C therapies. These molecules pose a particular challenge to make because their phosphorus atoms are chiral. While myriad methods for making chiral carbon are available, routes to chiral phosphorus are rare.

Tomislav Rovis, DiRocco’s doctoral mentor at Colorado State University, says DiRocco had the Midas touch as a graduate student. “Everything he did turned to gold. His chemical intuition was impeccable, and he had the unique ability to extract exactly the information he needed out of every reaction that he ran without getting distracted or wasting any time,” says Rovis, now at Columbia University. “It wasn’t luck but clarity of thought and a killer instinct.”

Three key papers

A Multifunctional Catalyst That Stereoselectively Assembles Prodrugs” (Science 2017, DOI: 10.1126/science.aam7936)

Late-Stage Functionalization of Biologically Active Heterocycles through Photoredox Catalysis” (Angew. Chem. Int. Ed. 2014, DOI: 10.1002/anie.201402023)

Catalytic Asymmetric Intermolecular Stetter Reaction of Heterocyclic Aldehydes with Nitroalkenes: Backbone Fluorination Improves Selectivity” (J. Am. Chem. Soc. 2009, DOI: 10.1021/ja904375q)

Stories in C&EN about DiRocco’s work:

Whipping phosphorus into chiral shape

Reactions may help drugmakers add ‘magic methyls’ more easily


DiRocco spoke at the American Chemical Society national meeting on Aug. 21 in Washington, D.C., about manufacturing medicines more efficiently and sustainably. Watch to hear him explain how he’s helping Merck scale up its output with innovative catalysts and high-throughput experimentation.
Credit: C&EN/ACS Productions

Vitals

Current affiliation: Merck & Co.

Age: 32

Ph.D. alma mater: Colorado State University

Advice for young scientists: “Try every idea and never talk yourself out of an experiment. Some of the most meaningful discoveries were the product of pure serendipity.”

Role model: Albert Einstein “for his humility in life and in science.”

Jillian Dempsey
Michael Feasel