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Phase Diagrams

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A phase diagram combines plots of pressure versus temperature for the liquid-gas, solid-liquid, and solid-gas phase-transition equilibria of a substance. These diagrams indicate the physical states that exist under specific conditions of pressure and temperature and also provide the pressure dependence of the phase-transition temperatures (melting points, sublimation points, boiling points). Regions or areas labeled solid, liquid, and gas represent single phases, while lines or curves represent...

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Updated: Jan 27, 2026

Solid-phase Synthesis of [4.4] Spirocyclic Oximes

Solid-phase Synthesis of [4.4] Spirocyclic Oximes

Published on: February 6, 2019

Liquid-Phase Oligonucleotide Synthesis: Past, Present, and Future Predictions.

Alejandro Gimenez Molina¹, Yogesh S Sanghvi²

¹Nucleic Acid Center, Department of Physics, Chemistry & Pharmacy, University of Southern Denmark, Odense, Denmark.

Current Protocols in Nucleic Acid Chemistry

|March 29, 2019

Summary

Large-scale manufacturing of therapeutic oligonucleotides is crucial. Liquid-phase oligonucleotide synthesis (LPOS) offers a scalable, cost-effective, and environmentally friendly alternative to traditional methods for meeting future demand.

Keywords:

DNA RNA large-scale synthesis liquid-phase oligonucleotide synthesis oligonucleotides phosphoramidites scale up soluble supports solution phase

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Last Updated: Jan 27, 2026

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Published on: October 25, 2019

Area of Science:

Medicinal Chemistry
Process Chemistry
Biotechnology

Background:

Therapeutic oligonucleotides represent a significant advancement in treating human diseases, with numerous candidates in clinical trials and several FDA-approved drugs.
Current manufacturing relies on solid-phase synthesis, which faces challenges in meeting projected metric ton quantities for advanced clinical trial products.

Purpose of the Study:

To review and summarize advances in liquid-phase oligonucleotide synthesis (LPOS) as a potential solution for large-scale oligonucleotide manufacturing.
To highlight innovative LPOS protocols and their potential for future production.

Main Methods:

Literature review of major efforts in developing LPOS technologies.
Analysis of existing and emerging LPOS protocols for scalability, cost-effectiveness, and environmental impact.

Main Results:

Significant progress has been made in developing LPOS technologies to address the scale-up challenge.
Ongoing efforts focus on creating efficient, green chemistry protocols for oligonucleotide manufacturing.

Conclusions:

LPOS presents a promising alternative strategy for the large-scale production of therapeutic oligonucleotides.
Future developments in LPOS aim for scalable, cost-effective, and environmentally benign manufacturing processes.