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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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slide4
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!
slide5
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”
slide6
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
slide7
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)

slide8
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
slide10
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
slide11
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
slide12
Repeat with L-alanine as a catalyst:

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

slide13

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

slide15

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

slide16
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!
slide19
 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