Optimization of steady state recycling parameters utilizing polarimetry in chiral separations

Processing gram to kilogram quantities of target analytes has led to the exploration of several high-throughput separation techniques. Among those investigated is steady state recycling (SSR). Similar to simulated moving bed (SMB) fractions are collected from the leading and trailing edges of a chromatographic profile while sample material is injected into the interior. Purifying large amounts of sample in the semi-preparative stage is ideal for these groups. SSR allows for development of methods capable of separating 50 g to kilograms and even greater amounts of product efficiently. Using polarimetry to optimize the SSR method further improves the efficiency of method development, providing comprehensive data leading to incisive development decisions. Accurate sample injection allowed continual 99% enantiomer separation after polarimetry optimization. We have developed an efficient SSR optimization methodology that offers rapid development of chiral separation by SSR.