What is the NUS capping-and-coupling strategy?

A photocatalytic method to directly couple unprotected native sugars with N-heteroarenes, forming C-heteroaryl glycosides in one step without protection groups. See Nature Synthesis paper .

Why are C-heteroaryl glycosides important?

They offer metabolic stability for antibiotics, anticancer agents, and mRNA vaccine components, outperforming O-glycosides.

How does photocatalysis enable this coupling?

Visible light activates a redox-active thioglycosyl intermediate, driving selective C-C bond formation via a novel radical pathway.

Who led the NUS research team?

Assoc Prof Koh Ming Joo (Chemistry) and Prof Chan Chun Yong Eric (Pharmacy), with students Qian-Yi Zhou and Daniel Ng.

What bioactivity was demonstrated?

A product inhibited glycogen breakdown 114x more than glucose, promising for type 2 diabetes therapy targeting hepatic glucose output.

Advantages over traditional glycosylation?

One-step, mild conditions, broad scope, high yields/stereoselectivity, scalable—no multi-step protection/deprotection.

Impact on Singapore biotech?

Bolsters NUS's role in a sector with S$25B funding, attracting pharma investment and talent. Singapore uni jobs booming.

What sugars and heteroarenes work?

Glucose, mannose, disaccharides; quinolines, indoles, pyrimidines—with 70-95% yields.

Late-stage drug modification, novel carbohydrates, integration with AI synthesis platforms.

Career paths in this field?

Postdocs, faculty in catalysis/pharma. Check NUS postdoc jobs or research roles .

Where was it published?

Nature Synthesis , Jan 19, 2026. NUS details .

NUS Photocatalysis Breakthrough: Capping-Coupling Strategy |

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The Revolutionary Capping-and-Coupling Strategy from NUS

In a groundbreaking advancement for organic synthesis, researchers at the National University of Singapore (NUS) have unveiled a novel 'capping-and-coupling' strategy that enables the direct photocatalytic coupling of native sugars with N-heteroarenes. This NUS photocatalysis breakthrough addresses longstanding challenges in creating C-heteroaryl glycosides, key building blocks in pharmaceuticals and vaccines. Traditional methods often require multiple protection and deprotection steps for the hydroxyl groups on sugars, making the process inefficient and wasteful. The new approach streamlines this into a single step under mild visible light conditions, opening doors to faster drug discovery. Schematic illustration of the NUS capping-and-coupling photocatalysis strategy linking native sugars to N-heteroarenes

Decoding the Science: How the Capping-and-Coupling Process Works

The capping-and-coupling strategy begins with selective activation at the anomeric C1 position of the native sugar. A temporary 'cap'—a bench-stable, redox-active thioglycosyl intermediate—is installed, protecting the sugar without affecting other hydroxyl groups. This intermediate is then exposed to an N-heteroarene, a photocatalyst, and visible light. The light drives a unique radical pathway, forging a robust carbon-carbon bond and yielding the C-heteroaryl glycoside. This pathway differs from prior photochemical activations, ensuring high stereoselectivity and broad substrate compatibility, including mono- and oligosaccharides like glucose, mannose, and cellobiose with quinolines, indoles, and pyrimidines.

Key advantages include gram-scale synthesis potential, no harsh reagents, and yields often exceeding 80%. For instance, coupling D-glucose with 4-methylquinoline achieved over 90% yield with excellent beta-selectivity, crucial for mimicking natural glycosidic linkages.

Meet the Minds Behind the NUS Photocatalysis Breakthrough

Leading the charge is Associate Professor Koh Ming Joo from NUS Department of Chemistry, a Dean's Chair Professor and NRF Investigator whose group specializes in sustainable catalysis. Collaborating closely is Professor Chan Chun Yong Eric from the Department of Pharmacy and Pharmaceutical Sciences, bringing expertise in medicinal chemistry. Key contributors include PhD students Qian-Yi Zhou and Daniel Zhi Wei Ng. Assoc Prof Koh noted, 'The most appealing way to make C-heteroaryl glycosides is to merge native saccharides with N-heteroarenes through direct C-C bond formation.' This interdisciplinary effort exemplifies NUS's strength in higher education research.Aspiring chemists can draw inspiration for academic CVs from such profiles.

Publication in Nature Synthesis: A Milestone for Singapore Research

The work, titled 'Photocatalytic coupling of unprotected sugars and N-heteroarenes,' appeared in Nature Synthesis on January 19, 2026 (DOI: 10.1038/s44160-025-00980-8). This high-impact journal underscores the strategy's novelty. For more details, visit the official press release or NUS Chemistry's announcement at NUS Chemistry.

Transforming Pharmaceutical Development with C-Heteroaryl Glycosides

C-heteroaryl glycosides feature in antibiotics, antitumor agents, and mRNA vaccine stabilizers like those for COVID-19. Their carbon linkage offers superior metabolic stability over oxygen-linked counterparts, resisting enzymatic cleavage. This NUS innovation accelerates late-stage glycosylation of complex drug scaffolds, potentially slashing development timelines from months to days. In drug discovery, where speed is critical, such tools are invaluable.Researchers seeking roles in pharma synthesis will find these advances compelling.

Antibacterial and antiviral properties in natural products like phloridzin analogs.
Anticancer activity via targeted glycoside mimics.
Enhanced vaccine efficacy through stable lipid nanoparticle coatings.

Biological Potency: A Leap in Glycogen Regulation

Beyond synthesis, the team evaluated bioactivity. One product inhibited glycogen breakdown 114 times more potently than its parent sugar, targeting glycogen phosphorylase—a key enzyme in hepatic glucose release. This holds promise for type 2 diabetes management, where excessive glycogenolysis contributes to hyperglycemia. Traditional inhibitors like CP-91149 show glucose-lowering in models; this glycoside could offer improved selectivity. Structure of potent C-heteroaryl glycoside from NUS research inhibiting glycogen breakdown

Singapore's Biotech Ecosystem and NUS's Pivotal Role

Singapore invests heavily in life sciences, with the biomedical sector contributing 2.6% to GDP and over S$25 billion in RIE 2025 funding. NUS, a top global university, drives this through hubs like the Centre for Sustainable Catalysis. This breakthrough bolsters Singapore's pharma hub status, attracting firms like Pfizer and fostering startups. For higher education, it highlights collaborative training in chemistry and pharmacy.Explore Singapore university opportunities amid this growth.

Challenges Overcome and Advantages in Photocatalytic Glycosylation

Past methods struggled with sugar reactivity and selectivity. The capping step neutralizes anomeric reactivity temporarily, while photocatalysis enables precise radical coupling under green conditions—no high heat or toxic metals. Compared to enzymatic glycosylation (limited scope) or metal-catalyzed (harsh), this is versatile and scalable.

Substrate scope: 20+ sugars, 30+ N-heteroarenes.
Efficiency: 70-95% yields, >20:1 dr in many cases.
Sustainability: Visible light, earth-abundant photocatalysts.

Future Outlook: Expanding Horizons in Carbohydrate Chemistry

Ongoing work at NUS aims to extend to other glycosides and complex natural products. Assoc Prof Koh envisions 'powerful avenues for late-stage glycosylations.' With AI-driven synthesis rising, photocatalysis like this could integrate into automated platforms. In Singapore, expect more NRF-funded innovations propelling biotech exports.

Career Insights for Aspiring Photocatalysis Researchers

This NUS photocatalysis breakthrough spotlights hot skills: organic synthesis, photochemistry, radical mechanisms. Graduates from NUS Chemistry or Pharmacy thrive in academia, pharma giants, or startups. Singapore offers research assistant jobs, postdocs, and faculty positions. Check postdoc opportunities or professor ratings for guidance. Platforms like higher ed career advice provide tips on entering this field.

Implications for Global Higher Education and Innovation

NUS exemplifies how focused investment yields world-class research, inspiring universities worldwide. For students, it underscores interdisciplinary PhDs in chemistry-pharma. Stakeholders—from policymakers to industry—see streamlined synthesis reducing costs, aiding affordable drugs. Actionable: Labs can adopt this protocol; educators integrate into curricula.

In summary, the capping-and-coupling strategy marks a paradigm shift, positioning NUS and Singapore at the forefront of sustainable chemistry. Explore university jobs, higher ed jobs, or rate your professors to join this exciting domain.