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

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


Imines in putative prebiotic synthesis of histidine

Imines in putative prebiotic synthesis of histidine:


The synthesis of dilantin also involves imines expt 7

Strecker synthesis


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:

    • 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?

    • 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

    • 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


The synthesis of dilantin also involves imines expt 7

  • 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


The synthesis of dilantin also involves imines expt 7

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


The synthesis of dilantin also involves imines expt 7

  • Repeat with L-alanine as a catalyst:

    Cordova, A et al. Chem. Commun.2005, 3586-3588


The synthesis of dilantin also involves imines expt 7

Mechanism:

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

Selectivity?


Selectivity

Selectivity?

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. 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

CO2H participates as acid


Enantioenrichment

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!


The synthesis of dilantin also involves imines expt 7

  •  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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