An intriguing example of how chirally enriched amino acids in the prebiotic world can generate sugars with D-configurati

1. Cordova et al. Chem. Commun., 2005, 2047-2049 • An intriguing example of how chirally enriched amino acids in the prebiotic world can generate sugars with D-configuration & with enantioenrichment: The Model: L-proline: a 2° amine; popular as an organocatalyst because it forms enamines readily

2. Mechanism: enamine formation CO2H participates as acid

4. Enantioenrichment % ee of sugar vs % ee of AA • Initially used 80% ee proline to catalyze reaction → >99% ee of allose • Gradually decreased enatio-purity of proline • Found that optical purity of sugar did not decrease until about 30% ee of proline! • Non-linear relationship!

5.  chiral amplification • % ee out >> % ee in! • Suggests that initial chiral pool was composed of amino acids • Chirality was then transferred with amplification to sugars → “kinetic resolution” • Could this mechanism have led to different sugars diastereomers? • Sugars →→ RNA world →→ selects for L-amino acids? • Small peptides?

6. Catalysis by Small Peptides • Small peptides can also catalyze aldol reactions with enantioenrichment (See Cordova et al. Chem. Commun. 2005, 4946) • Found to catalyze formation of sugars • It is clear that amino acids & small peptides are capable of catalysis i.e., do not need a sophisticated protein!

7. From Amino Acids  Peptides • Peptides are short oligomers of AAs (polypeptide ~ 20-50 AAs); proteins are longer (50-3000 AAs) • Reverse reaction is amide hydrolysis, catalyzed by proteases

8. At first sight, this is a simple carbonyl substitution reaction, however, both starting materials & products are stable: • RCO2- -ve charge is stabilized by resonance • Amides are also delocalized &  carbon & nitrogen are sp2 (unlike an sp3 N in an amine):

9. Primary structure: AA sequence with peptide bonds • Secondary structure: local folding (i.e. -sheet & -helix) -sheet  helix