Chiral Symmetry Breaking of Racemic 3-Phenylsuccinimides via Crystallization-Induced Dynamic Deracemization

Sanada, Kazutaka; Washio, Aoi; Nishihata, Kazuki; Yagishita, Fumitoshi; Yoshida, Yasushi; Mino, Takashi; Suzuki, Shinichi; Kasashima, Yoshio; Sakamoto, Masami

doi:10.1021/acs.cgd.1c01010

Cited by 10 publications

(8 citation statements)

References 53 publications

(50 reference statements)

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“…To develop such a spontaneous deracemization protocol, conglomerate crystallization conditions must be unified with racemization conditions such that both may occur simultaneously. Multiple strategies have been employed to allow for solution phase racemization while simultaneously crystallizing the target compound, including base catalysis, − acid catalysis, reversible reactions (such as the Mannich, aldol, , Diels–Alder, , [2,3]-sigmatropic rearrangements, annulation reactions), Schiff base formation, − photoracemization, and thermal racemization (such as crystallizing from a melt). With this established, a chiral symmetry breaking event is introduced to allow the system to spontaneously enantioenrich.…”

Section: Resultsmentioning

confidence: 99%

Identifying a Hidden Conglomerate Chiral Pool in the CSD

Walsh

Barclay

Begg

et al. 2022

JACS Au

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Conglomerate crystallization is the spontaneous generation of individually enantioenriched crystals from a nonenantioenriched material. This behavior is responsible for spontaneous resolution and the discovery of molecular chirality by Pasteur. The phenomenon of conglomerate crystallization of chiral organic molecules has been left largely undocumented, with no actively curated list available in the literature. While other crystallographic behaviors can be interrogated by automated searching, conglomerate crystallizations are not identified within the Cambridge Structural Database (CSD) and are therefore not accessible by conventional automated searching. By conducting a manual search of the CSD and literature, a list of over 1800 chiral species capable of conglomerate crystallization was curated by inspection of the racemic synthetic routes described in each publication. The majority of chiral conglomerate crystals are produced and published by synthetic chemists who seldom note and rarely exploit the implications this phenomenon can have on the enantiopurity of their crystalline materials. With their structures revealed, we propose that this list of compounds represents a new chiral pool which is not tied to biological sources of chirality.

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Section: Resultsmentioning

confidence: 99%

Identifying a Hidden Conglomerate Chiral Pool in the CSD

Walsh

Barclay

Begg

et al. 2022

JACS Au

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“…This unique approach has been shown to work with many chiral compounds, as summarized in Table 1. [36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55] F I G U R E 5 Schematic for the mechanism of attrition-enhanced deracemization. S and R represent the different absolute configuration of each enantiomer.…”

Section: Attrition-enhanced Deracemizationmentioning

confidence: 99%

“…This unique approach has been shown to work with many chiral compounds, as summarized in Table 1 36–55 . However, as with deracemization, the compound must be able to both racemize in solution and form a conglomerate.…”

Section: Attrition‐enhanced Deracemizationmentioning

confidence: 99%

Recent advances in the field of chiral crystallization

Putman

Armstrong

2022

Chirality

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Crystallization is one of the largest and most economical bulk purification techniques used in industry today. There has been an increase in demand for enantiomerically pure compound production for research, organic synthesis, pharmaceutical drug production, and other applications. Even after asymmetric synthesis, chiral purification will always be necessary. The focus of this review is on recent advances in chiral crystallization for the purification of enantiomers. A comprehensive discussion of three techniques and their mechanisms is provided, namely: attrition‐enhanced deracemization, cocrystallization, and inorganic ionic cocrystallization. Several examples of attrition‐enhanced deracemization are discussed. The key advantage of this technique is that it eliminates enantiomeric waste and can be used to produce enantiomeric excesses of greater than 99% from racemic mixtures. Chiral cocrystallization is examined, with over 60 cocrystallizing compounds, as an excellent means for enantiomeric enrichment. Selective chiral inclusion complexation was shown to be a novel approach for the formation of cocrystals. Chiral inorganic ionic cocrystallization is a new technique involving the formation of cocrystals between chiral ligands and certain metal salts in order to produce conglomerate crystal behavior in otherwise racemic compounds.

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“…This process differs from dynamic kinetic resolution in that no new product is formed, and the additional steps to remove the resolving agents from the products are not needed. 39,40 Thus, the method developed herein is more efficient as the substrateracemic amine and desired product-chiral amine possess an identical chemical structure.…”

Section: ■ Introductionmentioning

confidence: 98%

Deracemization of Racemic Amine Using ω-Transaminase and a Nickel-Based Nanocatalyst

Wang

Sun

et al. 2022

ACS Catal.

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Chiral amines are key building blocks for the development of numerous bioactive compounds. In this study, we developed a concurrent chemoenzymatic cascade approach using ω-transaminase for the isomeric configuration inversion of a racemic amine mixture. One isomer was transaminated using ω-transaminase, generating coproduct ketones and an additional chiral substance. Then, the mixture underwent selective reductive amination of a ketone using a specially designed compatible nickel-based nanocatalyst, which transformed coproduct ketone to racemic amines while leaving the opposite enantiomer unchanged. The combination of the two steps in one reaction system functions as an overall isomeric configuration inversion system. Moreover, the desired chiral amines with an additional chiral substance were formed. The procedure consumed NH3 and generated H2O as the sole byproduct.

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Chiral Symmetry Breaking of Racemic 3-Phenylsuccinimides via Crystallization-Induced Dynamic Deracemization

Cited by 10 publications

References 53 publications

Identifying a Hidden Conglomerate Chiral Pool in the CSD

Identifying a Hidden Conglomerate Chiral Pool in the CSD

Recent advances in the field of chiral crystallization

Deracemization of Racemic Amine Using ω-Transaminase and a Nickel-Based Nanocatalyst

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