Replication of α-amino acids via Strecker synthesis with amplification and multiplication of chiral intermediate aminonitriles

Abstract

Replication of chiral l- and d-α-(p-tolyl)glycine has been achieved in combination with the asymmetric induction, amplification and multiplication of their own chiral intermediates, l- and d-aminonitriles, in the solid-phase via the Strecker reaction between three achiral components, which is a plausible prebiotic mechanism for amino acid synthesis.

Highly Stereoselective Strecker Synthesis Induced by a Slight Modification of Benzhydrylamine from Achiral to Chiral

“…The tiny imbalance of the enantiomorphous aminonitriles could be greatly amplified from ca. 0.05 % enantiomeric excess ( ee ) to near enantiopure (>99.5 % ee ) by thermal dissolution/crystallization cycles . Although this transformation is powerful for the synthesis of large amounts of highly enantioenriched α‐aminonitriles—the chiral intermediates of α‐amino acids—crystallization of aminonitriles in the conglomerates is necessary.…”

Absolute asymmetric Strecker synthesis in a mixed aqueous medium: reliable access to enantioenriched α-aminonitrile

“…As noted, we have reported a significant amplification of the solid-state ee by thermally controlled repetition of partial dissolution and crystallization. 40 In our simulation, almost the same amount of L-and D-conglomerates 4 (racemate) was dissolved in the heating step; that is, the enantiomeric imbalance was concentrated in the residual solid 4. Subsequently, 4 was recrystallized at the gradual cooling step to keep the amplified (concentrated) ee of the residual 4, as rapid racemization occurred in the solution phase containing DBU.…”

“…36,37 Thus, self-disproportionation of enantiomers is a fundamental phenomenon to improve the enantiopurity of chiral compounds. 38 Our research focus includes Strecker-type synthesis [39][40][41][42] because this has been considered a possible prebiotic mechanism for α-amino acid synthesis since the seminal report on electric discharge experiments conducted under plausible prebiotic conditions. 3,43 The linkage between the origin of chirality and the formation of prebiotic amino acids may constitute a novel approach that can be used to explain the biological homochirality seen in L-amino acids.…”

“…Based on this concept, we have reported the spontaneous formation and amplification of enantioenriched α-aminonitriles forming conglomerates in methanol, in which the enantiomerically enriched product could be obtained 43 times out of a total of 160 experi-ments. 39 The solid-state ee of α-aminonitriles could be enhanced significantly 39,40 by Viedma ripening 5,30-33 and its modified method, i.e., temperature cycle. 34 As shown in Fig.…”

“…Here, we demonstrate that the Strecker reaction of three achiral reagents, hydrogen cyanide (HCN), 4 amine and aldehyde, in a mixed aqueous medium, gives enantioenriched α-aminonitrile with high ee without using any chiral sources. In addition, a previously reported amplification cycle by temperature control 40 could be used to induce the enantiomeric imbalances in the solid state to provide highly enantiomerically enriched aminonitriles, in which stochastic behavior was observed for the formation frequency of L-and D-enriched compounds.…”