Manganese makes its mark in drug synthesis
Rice lab finds common metal more efficient at catalyzing pharma building blocks

Date:
October 5, 2021
Source:
Rice University
Summary:
Chemists find manganese far superior to silver and cerium as a
way to make building blocks for drug design and manufacture.



FULL STORY ==========================================================================
Just because you've solved a standing chemistry challenge doesn't mean
you can't make it better. Rice University scientists had that in mind
when they set out to improve their technique to make a common building
block for drugs.


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Rice chemist Julian West and graduate student Yen-Chu Lu found that
an Earth- abundant salt of manganese further simplifies the process
of synthesizing fluoroketones, precursor molecules for drug design
and manufacture.

The complex method required catalysts of expensive silver until the West
lab figured out how to replace it with a cerium-based compound. That in
turn led the researchers to eye manganese as a next-level catalyst.

The lab reported its results in the American Chemical Society journal
ACS Catalysis.

Attaching negatively charged fluorine atoms to ketones, biological
compounds with a variety of structures, helps direct the functional groups toward desired reactions when used in anticancer and other compounds,
West said. He noted in the previous study that replacing hydrogen atoms
with fluorines "is like armor plating at that position" and helps drugs
last longer in the body.

Manganese has several advantages over cerium, West said, and not just
for its easy availability and low cost.



==========================================================================
"The amount of product we got with cerium was good, but for it to work, we
had to use as much cerium as starting material," said West, an assistant professor of chemistry. "With manganese, we required less than a 10th as
much catalyst - - and more importantly, it just works better. We would
rather use a trace amount of catalyst to save on material costs and to
simplify purification." And while cerium was able to promote reactions
with relative efficiency, it was essentially one-and-done.

Cerium can be recycled for reuse as a catalyst but it requires a
difficult reoxidization. That turned out to be much easier with manganese salts. "Yen-Chu found the reagent we use, Selectfluor, reoxidizes the
manganese enough to react again and again," he said.

Manganese is also cheap enough that recycling the material may not be
cost effective for manufacturers, West said.

The only downside, he said, is that manganese-enabled reactions can
take several hours to produce a batch of molecules as opposed to the
half-hour or so needed by cerium. But even that limitation should prove
no obstacle because of the relative cost, he said.

"In our view, that's a fair tradeoff, because you're reducing the amount
of reagents you need to add and getting more of the compound that you
want," West said.

He said head-to-head comparisons with silver catalysts proved manganese delivered more product molecules with half the amount of catalyst. "So I
think we're getting to state-of-the-art catalysis with this reaction."
The Cancer Prevention and Research Institute of Texas (RR190025) and
the Robert A. Welch Foundation (C-2085) supported the research.

========================================================================== Story Source: Materials provided by Rice_University. Note: Content may
be edited for style and length.


========================================================================== Journal Reference:
1. Yen-Chu Lu, Julian G. West. C-C Bond Fluorination via Manganese
Catalysis. ACS Catalysis, 2021; 12721 DOI: 10.1021/acscatal.1c03052 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211005124714.htm

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