1. The synthesis of Dilantin also involves imines (expt 7):

2. Imines in putative prebiotic synthesis of histidine:

3. Strecker synthesis

4. Interestingly, AA’s have been detected in space: Murchison Meteorite: –Murchison, Australia (1969) –Contained noble gases & insoluble material such as graphite & silicates –Also contained several organics: –Dicarboxylic acids, alkanes & amino acids Contained gly, ala, glu & non-proteinegenic AA’s (isovaline → most abundant) Components found in Urey-Miller Exp’t!! –Origin in space? Isotopic distribution indicates amino acids were extraterrestrial in origin i.e., Natural abundance of 15 N is 0.37%, however, meteorites were found to have +50% to 93% –Majority of AA’s were racemic, but some did show slight enantiomeric excess (L) (1-15%) –  there is enrichment!

5. There had to be a natural process that separated & concentrated one enantiomer over the other → chiral selection Mechanism of enrichment? a)Circularly polarized light from stars: This CPL is in the UV & IR range & is chiral  CPL can form or destroy the two enantiomers of an AA at different rates → asymmetric photolysis Could have led to enrichment of L-amino acids in meteorite b)Selection by crystal faces: Most minerals are centric → do not display handedness Calcite, CaCO 3, (exception) displays surfaces that have a mirror relationship → “chiral-like”

6. Hazen exp’t: –Immersed large crystal of calcite in a dilute solution of 50:50 D,L- aspartic acid –GC analysis found that calcite absorbs different enantiomers on different surfaces

7. Enantioenrichment? –If one face proceeds forward, while the other is chemically inert, then we get enantioenrichment i.e., one face is exposed to light or one face is immersed (by chance) in water **Does calcite promote amino acid chain formation? Whatever the origin of homo-chirality, the ee was likely low However, once one AA is present in excess, then enantioenrichment can occur: Via Serine octamer (Cooks et al,. Angew. Chem. Int. Ed., 2003, 42, 3521) Enrichment by sublimation (Feringa et al,. Chem. Commun., 2007, 2578)

8. i.Serine octamer forms a non-covalent homochiral octamer in a mass spectrometer via electrospray ionization Octamer was found to be chiroselective—formed from enantiopure samples, but not racemic ones!  one L-serine selects to bind with 7 more L-enantiomers Also found that they could incorporate more than one type of AA—providing that all of the amino acids had the same chirality Additionally, octamer forms adducts enantioselectively with D-glyceraldehyde → could help explain relationship between L-amino acids in proteins & D-sugars as the dominant species in nature! Serine cluster also catalyzed dimerization of glyceraldehyde giving a C 6 sugar Cluster also found to bind to PO 4 3- and some metals

9. Serine Octamers

10. ii.Enrichment by sublimation Took mixtures of AA’s (leu, ala, phe, etc.) with low ee (~9%) & partially sublimed sample Results showed that in each case there was enrichment of the enantiomer (20-80%)! Indicates that a heat source may suffice for enantiomeric enrichment: Meteorites could be subjected to high temperatures that could result in enrichment

11. Another mechanism for enantioenrichment: organocatalysis via the aldol reaction Several years ago is was found that amino acids can catalyze reactions Recently “re-invented” as organocatalysts (as opposed to organometallic catalysts → Pd(PPh 3 ) 4, RuR 6, AlR 3,etc) Like the reactions we have seen already, it involves imines & their enamine tautomers For example in the aldol reaction: Rxn is diastereoselective but racemic

12. Repeat with L-alanine as a catalyst: Cordova, A et al. Chem. Commun. 2005, 3586-3588

13. Chirality in the enamine is transferred to the new chiral centres in the aldol Selectivity? Mechanism:

14. Selectivity? Proposed to occur via a 6-membered TS: Chirality in the enamine is transferred to the 2 new chiral centres in the aldol

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

16. Mechanism: enamine formation CO 2 H participates as acid

18. 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! % ee of sugar vs % ee of AA Enantioenrichment

19.  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? Alternative: small peptides