Flow synthesis of natural products: Ascorbic acid and N5-OH-L-Ornithine synthesis

Flow synthesis has emerged as a transformative approach in pharmaceutical manufacturing, offering unique control over reaction parameters, enhanced safety, and improved efficiency. This transformation from traditional batch processes to flow systems has the potential to revolutionize the production of vital compounds, addressing the growing demand for sustainable and cost-effective manufacturing methods in the pharmaceutical industry. This study explored the application of flow chemistry to two distinct yet equally important synthetic targets: L-ascorbic acid (vitamin C) and N5-OH-Ornithine, a key intermediate in piperazic acid synthesis. The goal was to develop more efficient and scalable routes to these compounds, which play crucial roles in nutrition and drug development. For L-ascorbic acid synthesis, the study adapted a modified Reichstein process from batch to flow conditions. Starting with D-glucose, four of the five steps, reduction, protection, oxidation, and lactonization, were successfully implemented in flow systems. These steps showed improved yields and shorter reaction times compared to batch methods. The second step, enzymatic oxidation, remains under investigation. The secondary objective, protecting L-Ornithine in the flow, faced challenges due to foaming and CO2 evolution, which caused clogging in the flow system. Strategies to address these challenges include larger tubing, continuous stirred tank reactors, and liquid-gas separators. Success with L-ascorbic acid synthesis highlights the power of flow synthesis in improving reaction efficiency and product yield. In contrast, the challenges encountered in L-Ornithine protection highlights the complexities of gas-evolving reactions in flow systems. This work contributes to the growing knowledge of applying flow chemistry in natural product synthesis.