Small molecules are still the most common
form of modern medicine. Their relatively
simple structures, oral availability, and costeffective
manufacturing make them indispensable
in global healthcare. Synthetic chemistry
underpins every stage of small molecule development,
from the earliest design efforts to
large-scale production.
In the discovery phase, researchers use synthetic
methods to rapidly probe structure–activity
relationships, where subtle changes to a
molecule’s structure can profoundly alter its
potency, selectivity, or safety. They employ
scaffold hopping to reconfigure a compound’s
core framework and introduce functional group
modifications that fine-tune solubility, stability,
and metabolic profile. These iterative cycles of
design and synthesis fuel the design–make–test–
decide cycle central to drug discovery (4).
Synthetic chemistry also makes it possible
to generate vast and diverse libraries of compounds
for high-throughput screening, a process
that identifies starting points for drug
development. Once a promising candidate
emerges, synthetic chemists refine and scale
the process to ensure reproducibility and
efficiency in manufacturing.
The approval of Suzetrigine, a non-opioid
analgesic, in 2025, highlights the central role
of modern synthesis (5). Through rational design,
researchers optimized a sodium channel
blocker that balanced high potency with minimal
off-target effects. They combined classical
transformations with modern catalytic and
protective group strategies to assemble the
molecule’s complex structure. This approach
illustrates how chemists blend and integrate
traditional methods with contemporary innovations
to achieve therapeutic goals.
Classic synthetic
chemistry
Solid-phase
synthesis
Cross-coupling
reactions
Modern synthetic
chemistry
19th Century 20th Century Present
New synthetic methods Design and planning tools New synthetic paradigms
Automated synthesis
platforms
AI-assisted design Molecular editing
Electrochemical Synthesis
Enzymatic chemistry Flow chemistry
Photoredox Catalysis Cheminformatics platforms High throughput experimentation
Modern toolbox of synthetic chemistry
Not all medicines come from nature’s playbook.
While plants and microbes have yielded life-saving
compounds, many modern drugs are built from
scratch or adapted by chemists through synthetic
chemistry. This discipline enables the purposeful
construction of molecules, shaping discoveries
from aspirin to today’s targeted therapies. As new
modalities and data-driven approaches emerge,
its adaptability makes it remain central to pharmaceutical
innovation.
How is synthetic
chemistry driving drug
discovery today?
Design
Small
molecule drugs
Analyze & Decide
Make
Test
Turning ideas into synthesizable molecules
• Scaffold and functional group design
• Retrosynthetic planning
• Molecular modelling
Refining molecules through chemistry insights
• SAR/SPR analysis
• Adjust synthetic strategy
Synthesizing candidate compounds
• Develop synthetic routes
• Execute target molecule synthesis
Providing compounds for evaluation
• ADME profiling
• Biological assays
• Physicochemical tests
Does synthetic chemistry still matter
in modern drug discovery?
Evolving alongside new modalities and digital
technologies, synthetic chemistry continues to be the
driving force behind modern and future medicines.
Synthetic chemistry emerged in the 19th century
as chemists began assembling molecules
from simple building blocks. The synthesis of
urea in 1828 challenged the notion that organic
compounds could only come from living organisms
(1). Throughout the 19th and early 20th centuries,
chemists steadily expanded their toolkit,
building dyes, analgesics, and antibiotics that
transformed medicine (2).
The 20th century brought breakthroughs that
reshaped the field. Solid-phase peptide synthesis,
introduced in the 1960s, allowed chemists to
build peptides step by step with efficiency. In the
following decades, cross-coupling reactions provided
robust methods to form carbon–carbon
bonds, vastly expanding access to chemical space
(3). These developments set the stage for the exploration
of entirely new types of molecular scaffolds
and the fine-tuning of drug-like properties.
Far from fading, the field has continued to reinvent
itself in the 21st century. Today’s chemists
wield new techniques: molecular editing allows
subtle, late-stage modifications to drug candidates;
enzymatic catalysis harnesses nature’s
machinery for more selective reactions; and photoredox
chemistry uses light to trigger bond formations
once thought impossible (3).
At the same time, digital tools have revolutionized
design and planning. Artificial intelligence
now assists retrosynthesis, cheminformatics platforms
map chemical space, and automated synthesis
systems execute complex multistep reactions
with minimal human intervention (3). Rather
than being eclipsed by new modalities, synthetic
chemistry has enabled them and remained an
evolving engine at the heart of drug discovery.
Why is synthetic chemistry essential for
small molecule drug development?
