The origin of biological homochirality, such as seen in L-amino acids and D-sugars, has been a puzzle of broad interest. Several theories have been proposed for the origin of homochirality. However, the enantioenrichments induced by these mechanisms have been very low, and a linkage to the high enantioenrichments of biomolecules is missing.
Asymmetric autocatalysis is a reaction in which a chiral product acts as a chiral catalyst for its own production. In 1995, Kenso Soai discovered asymmetric autocatalysis with significant amplification of enantiomeric excess (ee). Pyrimidyl alkanol acts as an asymmetric autocatalyst in the enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde to produce more of itself with the same absolute configuration. Starting from the asymmetric autocatalyst, i.e., pyrimidyl alkanol, with extremely low ee (ca. 0.00005%), three consecutive asymmetric autocatalyses using the product as the asymmetric autocatalyst for the next round amplified the ee to > 99.5% ee with a significant multiplication of the amount by a factor of ca. 630,000 times. The reaction has established the existence of a real chemical process in which a chiral compound with an extremely tiny ee automultiplies with significant amplification of ee, leading to an essentially enantiopure compound. This unique reaction has been named the Soai reaction. The impact of Soaifs asymmetric autocatalysis on the study of the origins of chirality has been very strong. The Soai reaction enables correlation of the origins of chirality, for example, quartz and circularly polarized light (CPL), to the highly enantioenriched pyrimidyl alkanol with the corresponding absolute configurations.
By using the Soai reaction, Soai has made significant contributions in elucidating the origins of chirality and homochirality. The reaction provides significant insights into the origin of homochirality in biomolecules. His contributions are as follows:
(1) Spontaneous absolute asymmetric synthesis.
Soaifs unique asymmetric autocatalysis enabled the first spontaneous absolute asymmetric synthesis. The initial fluctuation in enantiomeric balance in the reaction between pyrimidine-5-carbaldehyde and diisopropylzinc without the intervention of any chiral material was significantly amplified by the mechanism of asymmetric autocatalysis to afford (R)- or (S)-pyrimidyl alkanol with well above the detectable level of ee. The formation of (R)- or (S)-pyrimidyl alkanol exhibits a stochastic distribution. For years, it had been well accepted that the reaction between achiral compounds without the intervention of any chiral compound affords equal amounts of enantiomers, i.e., a racemic product. Soaifs absolute asymmetric synthesis has refuted this common belief.
(2) Chiral inorganic crystals such as quartz and chiral crystals formed from achiral organic compounds act as chiral initiators of asymmetric autocatalysis.
Soai found that chiral inorganic crystals such as d- and l-quartz and sodium chlorate serve as chiral initiators of asymmetric autocatalysis. The correlation between the chirality of the inorganic crystals and the chirality of organic compounds with very high ee was established for the first time. Chiral crystals formed from achiral organic compounds such as cytosine, hippuric acid, benzyl and tetraphenylethylene also work as chiral initiators of asymmetric autocatalysis to afford pyrimidyl alkanol with high ee.
(3) Asymmetric autocatalysis initiated by CPL.
Left- and right-CPL has been proposed as the origin of chirality, although the enantiomeric imbalance induced by CPL has been very low. Soai found that after irradiation of a racemic pyrimidyl alkanol with CPL, the subsequent asymmetric autocatalysis afforded pyrimidyl alkanol with > 99.5% ee with the corresponding absolute configurations correlated with the chirality of the CPL. The result stands as the first example of the correlation between the direction of CPL and the highly enantioenriched chiral compound.
(4) Asymmetric induction by chiral compounds arising from isotope substitution and by cryptochiral compounds.
Soai found that chiral compounds arising from carbon 13 substitution act as chiral initiators and induce asymmetry in the addition of i-Pr2Zn to pyrimidine-5-carbaldehyde to afford highly enantioenriched pyrimidyl alkanol with the corresponding absolute configurations as those of the C13 chiral compounds. Soai also found that chiral amino acids and primary alcohols act as chiral initiators as a result of deuterium substitution.
Butylethylhexylpropylmethane is a chiral saturated quaternary hydrocarbon. However, it is known that the compound does not exhibit any detectable optical rotation, thus the compound is cryptochiral. By using the cryptochiral compound, asymmetric autocatalysis was found to discriminate the chirality of the compound. Cryptochiral isotactic polystyrene was successfully discriminated.
In addition, Soai reported the formation of chiral cytosine crystals of desired chirality from the chiral cytosine hydrate crystal by dehydration from a specific face. He also found the reverse phenomenon of the sense of enantioselectivity by the presence of an achiral catalyst.
As has been described above, the Soai reaction provides the clue to clarifying the origin of chirality and homochirality. The implication of the Soai reaction has expanded beyond organic synthesis, and the reaction has been cited not only in chemistry journals but also in various journals of physics, biology, origin of life, and space science. This shows that the Soai reaction has attracted extremely broad interest.