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

The synthesis of Dilantin also involves imines (expt 7):. Imines in putative prebiotic synthesis of histidine:. Strecker synthesis. Interestingly, AA’s have been detected in space: Murchison Meteorite: Murchison, Australia (1969)

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

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  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 15N 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? • 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 • Selection by crystal faces: • Most minerals are centric → do not display handedness • Calcite, CaCO3, (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. 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 C6 sugar • Cluster also found to bind to PO43- and some metals

  9. Serine Octamers

  10. 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: organocatalysisvia 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(PPh3)4, RuR6, AlR3,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. Mechanism: Chirality in the enamine is transferred to the new chiral centres in the aldol Selectivity?

  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. 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

  16. Mechanism: enamine formation CO2H participates as acid

  17. 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!

  18.  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

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