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

  • 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!


The synthesis of dilantin also involves imines expt 7

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”


The synthesis of dilantin also involves imines expt 7

  • Hazen exp’t: concentrated one enantiomer over the other

    • 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


The synthesis of dilantin also involves imines expt 7

  • Enantioenrichment? concentrated one enantiomer over the other

    • 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)


The synthesis of dilantin also involves imines expt 7

  • Serine octamer concentrated one enantiomer over the other

    • 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


Serine octamers
Serine Octamers concentrated one enantiomer over the other


The synthesis of dilantin also involves imines expt 7

  • Enrichment by sublimation concentrated one enantiomer over the other

    • 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


The synthesis of dilantin also involves imines expt 7

Another mechanism for enantioenrichment: concentrated one enantiomer over the other 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


The synthesis of dilantin also involves imines expt 7


The synthesis of dilantin also involves imines expt 7

Mechanism: concentrated one enantiomer over the other

Chirality in the enamine is transferred to the new chiral centres in the aldol

Selectivity?


Selectivity
Selectivity? concentrated one enantiomer over the other

Proposed to occur via a 6-membered TS:

Chirality in the enamine is transferred to the 2 new chiral centres in the aldol


The synthesis of dilantin also involves imines expt 7

Cordova et al. concentrated one enantiomer over the other 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


The synthesis of dilantin also involves imines expt 7

Mechanism: enamine formation concentrated one enantiomer over the other

CO2H participates as acid


Enantioenrichment
Enantioenrichment concentrated one enantiomer over the other

% 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!


The synthesis of dilantin also involves imines expt 7

  •  chiral amplification concentrated one enantiomer over the other

    • % 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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