Synthesis of Nucleosides & Nucleotides

Focused expertise in the synthesis of highly modified nucleosides, nucleotides, phosphoramidites, phosphoramidates, and triphosphates for antiviral, anticancer, and nucleic acid-based therapeutic programs that demand the highest standards of structural integrity and purity.

15+

years of nucleoside
synthesis expertise

1,500+

Track Record of highly modified nucleosides

key nucleotide modalities:
Phosphoramidite, phosphoramidate, triphosphate

01 — WHAT MAKES US DIFFERENT

Nucleosides and nucleotides are among the most structurally demanding targets in medicinal chemistry. The chemistry is challenging: stereoselective glycosylation, selective protection and deprotection of hydroxyl and amino groups, phosphorylation under anhydrous conditions, and the installation of non-natural modifications to base or sugar moieties all require a depth of expertise that generalist CROs cannot reliably provide. At Oxeltis, nucleoside synthesis has been at the core of our chemistry for over 15 years, and more than 1,500 highly modified nucleosides have been delivered to pharmaceutical and biotech partners worldwide.

Our expertise spans the full structural landscape: natural nucleosides and their analogs, carbocyclic and acyclic nucleosides, locked nucleic acid (LNA) analogs, 2'-modified ribonucleosides for oligonucleotide therapeutics, and modified nucleobases for probe chemistry and diagnostic applications. We further extend this capability into activated nucleotide derivatives, phosphoramidites for oligonucleotide assembly, ProTide-type phosphoramidates for prodrug programs, and nucleoside triphosphates for enzymatic assays and mechanism-of-action (MoA) validation studies.

Key differentiators

15+ years of dedicated nucleoside chemistry

Over 1,500 highly modified nucleosides synthesized, spanning antiviral, anticancer, diagnostic, and oligonucleotide applications

Full nucleotide activation capability

Phosphoramidites, phosphoramidates (ProTide), and triphosphates in-house

Expert stereoselective glycosylation and anomeric control

Resolving the selectivity challenges that define nucleoside synthesis difficulty

Scalable
routes

From mg (SAR) to multi-gram (preclinical/IND), with SFC-confirmed purity at every scale

02 — CAPABILITIES

The challenges we solve and how

From modified nucleosides to fully activated nucleotide derivatives, our synthesis capabilities cover the complete spectrum required for modern antiviral, anticancer, and oligonucleotide therapeutic programs.

Modified Nucleosides & Analogs

Custom modification of base or sugar moieties —methylation, fluorination, 2'-OH modifications (OMe, F, LNA), carbocyclic analogs, acyclic analogs, and non-natural nucleobases. Stereoselective glycosylation with anomeric control for both N- and C-nucleosides. Applications: antiviral APIs, anticancer nucleoside analogs, epigenetic probes, diagnostic tools

Phosphoramidites

Synthesis of Fmoc- and DMT-protected phosphoramidite of modified building blocks for the automated solid-phase assembly of oligonucleotides for therapeutic ASO and siRNA programs. Applications: oligonucleotide synthesis, ASOs, siRNA, mRNA cap analogs, gene editing tools

Phosphoramidates (ProTide)

ProTide-type phosphoramidate prodrugs masking the first phosphorylation step of nucleoside analog activation, improving membrane permeability, circumventing kinase-dependent activation, and delivering the nucleoside monophosphate intracellularly with enhanced bioavailability. Applications: antiviral prodrugs (e.g. Sofosbuvir-type), anticancer prodrug programs, intracellular delivery

Nucleoside Triphosphates (NTPs)

Synthesis of natural and modified NTPs for enzymatic studies, polymerase screening, and mechanism-of-action (MoA) validation of nucleoside analog inhibitors. Applications: polymerase assays, PCR, sequencing, MoA validation of antiviral/anticancer candidates, structural biology

Equipment & technology highlights

Flow chemistry platform
Photochemistry reactor
Mechanochemistry (ball milling)
High-performance SFC (analytical & preparative)
Transition metal catalysis toolkit
LC-MS (analytical & preparative)
HRMS
NMR (¹H, ¹³C, 2D)

Need a specialist partner for nucleoside or phosphoramidites building block synthesis?

From a non-commercially modified phosphoramidite building block for oligonucleotide project to a complex lead optimization program of highly modified nucleoside for antiviral — tell us about your project and we'll come back to you within 48 hours.