Scaling Up Attrition-Enhanced Deracemization by Use of an Industrial Bead Mill in a Route to Clopidogrel (Plavix)

Chiral Symmetry Breaking in Peptide Systems During Formation of Life on Earth

“…As such, we would like now to limit our consideration to just one amino acid, which we denote here as A for left enantiomer and as a for right enantiomer. We combine several well-known models described in the literature (Frank 1953;Avetisov and Goldanskii 1996;Plasson et al 2004Plasson et al , 2007Saito and Hyuga 2004;Weissbuch et al 2005;Brandenburg et al 2007;van der Meijden et al 2009;Noorduin et al 2010;Blackmond 2011;Coveney et al 2012;Hein et al 2012;Ribó et al 2013;Konstantinova 2013, 2014) and then study which combinations can possibly result in the symmetry breaking under the conditions of weak enantioselectivity of all relevant reactions. Even though the minimum interesting peptide length is three, we consider peptide chains up to length five in order to study how the increase in peptide length influences the symmetry breaking.…”

“…The number of works in this area could be made a subject of a separate research. Vast number of models of chiral symmetry breaking were proposed over the years and numerous experiments were performed, for example (Frank 1953;Avetisov and Goldanskii 1996;Plasson et al 2004Plasson et al , 2007Saito and Hyuga 2004;Weissbuch et al 2005;Brandenburg et al 2007; van der Meijden et al 2009;Noorduin et al 2010;Blackmond 2011;Coveney et al 2012;Hein et al 2012;Ribó et al 2013;Konstantinova 2013, 2014), and many others. However, most, if not all, theories and experiments related to chiral symmetry breaking during formation of life on Earth considered only a very limited number of substances and reactions, whereas the actual number of possible substances and reactions among them must have been extremely large, as we will soon discuss.…”

“…Alternative models of chiral symmetry breaking are based on inter-conversion of enantiomers. These models can be grouped into two classes: the models based on epimerization (Plasson et al 2004(Plasson et al , 2007Weissbuch et al 2005;Brandenburg et al 2007) and the models based on the deracemization process (Hein et al 2012;van der Meijden et al 2009;Noorduin et al 2010).…”

“…On the opposite side, deracemization utilizes a phase transition process of crystallization and nonlinearity due to the rate of crystallization being proportional to the surface area of the crystals (Hein et al 2012;van der Meijden et al 2009;Noorduin et al 2010). In contrast to basic chemical reactions, which are polynomial functions of concentrations, a phase transition, if viewed as a mathematical function, exhibits some discontinuity.…”

Resolution of Omeprazole Using Coupled Preferential Crystallization: Efficient Separation of a Nonracemizable Conglomerate Salt under Near-Equilibrium Conditions

“…So far, attrition-enhanced deracemization has been applied in the synthesis of enantiopure esters of naproxen 4 as well as the key chiral intermediate required in the preparation of clopidogrel (Plavix). 6,7 Attrition-enhanced deracemization is limited, however, to target molecules that are conglomerates and which can be racemized in solution in the presence of a stable crystalline phase. For those conglomerates that cannot be racemized most in factresolution by preferential crystallization, also an approach free of any resolving agent, can often be applied to isolate the pure enantiomers.…”