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ð2Þ
Thus, increased structural complexity gave higher enantioselec-
tivity. In a prebiotic scenario, amino acids formed on Earth or
brought to it by comets and meteorites condensed nonenzymati-
cally to form peptide oligomers.13,17 Next, the peptides catalyzed
the asymmetric formation of sugars that could form the backbones
of ancient RNA.18
8 For the proline-catalyzed intermolecular aldol reaction see: Z. G. Hajos
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In summary, we have demonstrated for the first time that
peptides and their analogues with a primary amino acid at the
N-terminus can be employed as highly stereoselective catalysts for
the direct asymmetric intermolecular aldol reaction. This will
dramatically expand the structural diversity and modularity in the
design and combinatorial construction of novel organocatalysts. A
peptide library based on the simple amino acids alanine and valine
catalyzed the asymmetric formation of the desired aldol products
in high yield and up to 99% ee. The peptide-catalyzed reactions are
accelerated by water, and are inexpensive, operationally simple and
environmentally benign. We also found that ancient peptides have
an intrinsic ability to catalyze the asymmetric neogenesis of sugars
under prebiotic conditions, which may explain the initial molecular
evolution of aldolase enzymes. Further expansion of peptide
catalysis in organocatalytic asymmetric C–C bond-forming reac-
tions, combinatorial catalyst preparation and density functional
theory calculations are ongoing.
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We gratefully acknowledge the Swedish National Research
Council, Carl-Trygger Foundation, Lars-Hierta Foundation
and Wenner-Gren Foundation for financial support and
Prof. H. Adolfsson for a generous gift of val-phenylalaninol.
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4948 | Chem. Commun., 2005, 4946–4948
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