Design and dynamic modeling of simulated moving bed processes for multicomponent biochemical separations

Four-zone simulated moving bed (SMB) processes have been used widely for isolating two pure products from two-component mixtures under ideal (high-efficiency) conditions. In many such cases, the uptake of solutes on the sorbent is described by a linear distribution coefficient. But many systems require the separation of more than two components, are operated under nonideal (low-efficiency) conditions, or have nonlinear uptake. In light of these challenges, generalized design strategies were investigated here for splitting multicomponent mixtures. The “standing wave” analysis for binary mixtures [76] was extended in this study to achieve any specified split of a mixture containing three or more components under nonideal conditions. Aspects of multicomponent fractionation and gradient were isolated and studied systematically. A four-component mixture of glucose, xylose, acetic acid, and sulfuric acid was chosen as an example to illustrate strategies for continuous multicomponent fractionation in a nonideal, linear system. This multicomponent fractionation strategy was validated on a laboratory-scale, low-pressure SMB system for the separation of three amino acids. These approaches point the way to a design procedure for SMB fractionation of a multicomponent, nonlinear, nonideal system with thermal gradients. Rate model simulations confirm that the standing wave design guarantees high purity and high yield for these separations

P(III) vs. P(V): A P(V) Reagent for Thiophosphoramidate Linkages and Application to An Asymmetric Synthesis of a Cyclic Dinucleotide STING Agonist

A highly stereoselective synthesis of a cyclic dinucleotide (CDN) STING agonist containing two chiral thiophosphoramidate linkages is described. These rare, yet key functional groups were, for the first time, installed efficiently and with high diastereoselectivity using a specially designed P(V) reagent. By utilizing this strategy, the CDN was prepared in greater than sixteen-fold higher yield than the prior P(III) approach, with fewer hazardous reagents and chromatographic purifications