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An intriguing example of how chirally enriched amino acids in the prebiotic world can generate sugars with D-configuration & with enantioenrichment:.


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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:
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Cordova et al. Chem. Commun ., 2005 , 2047-2049 An interesting case of how chirally advanced amino acids in the prebiotic world can produce sugars with D-arrangement & with enantioenrichment: The Model: L-proline: a 2 ° amine; mainstream as an organocatalyst in light of the fact that it shapes enamines promptly

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Mechanism: enamine development CO 2 H partakes as corrosive

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Enantioenrichment % ee of sugar versus % ee of AA Initially utilized 80% ee proline to catalyze response → >99% ee of allose Gradually diminished enatio-virtue of proline Found that optical immaculateness of sugar did not diminish until around 30% ee of proline! Non-direct relationship!

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 chiral intensification % ee out >> % ee in! Recommends that beginning chiral pool was made out of amino acids Chirality was then exchanged with intensification to sugars → “kinetic resolution” Could this component have prompted diverse sugars diastereomers? Sugars →→ RNA world →→ chooses for L-amino acids? Little peptides?

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Catalysis by Small Peptides Small peptides can likewise catalyze aldol responses with enantioenrichment ( See Cordova et al. Chem. Commun . 2005 , 4946) Found to catalyze development of sugars It is clear that amino acids & little peptides are equipped for catalysis i.e., needn't bother with a modern protein!

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From Amino Acids  Peptides are short oligomers of AAs (polypeptide ~ 20-50 AAs) ; proteins are longer (50-3000 AAs) Reverse response is amide hydrolysis, catalyzed by proteases

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right away, this is a basic carbonyl substitution response, on the other hand, both beginning materials & items are steady : RCO 2 - ve charge is balanced out by reverberation Amides are likewise delocalized &  carbon & nitrogen are sp 2 (not at all like a sp 3 N in an amine) :

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Primary structure: AA succession with peptide bonds Secondary structure: neighborhood collapsing (i.e. -sheet & -helix) -sheet  helix

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Amide bond: Formation & Degradation Thermodynamics Overall rxn is ~ thermoneutral ( Δ G ~ 0) Removal of H 2 O can drive response to amide arrangement In watery arrangement, response favors corrosive Kinetics Very moderate response Forward:

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Reverse: T.I = tetrahedral middle of the road Reaction Coordinate Diagram: TS 2 TS 1 Δ G Charge detachment No reverberation  HIGH ENERGY! T.I Large E A for forward response E An E A Large E A for converse response

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How would we conquer the hindrance? Warmth First “biomimetic” combination Disproved Vital power hypothesis But, cells work at an altered temperature! Initiate the corrosive: Activated corrosive

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Activation of carboxylic corrosive e.g. (Inorganic compound raises vitality of corrosive) Activation of carboxylic corrosive (towards nucleophilic assault) is a standout amongst the most widely recognized routines to shape an amide (peptide) bond - in nature & in synthetic union! Why is the vitality (of corrosive) raised?

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Recall carboxylic corrosive subsidiary reactivity: Depends on leaving gathering: Inductive impacts (EWG) Resonance in subordinate Leaving gathering capacity Nature utilizes acyl phosphates, esters (ribosome) & thioesters (NRPS)—more on this later

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Catalysis Lowering of TS vitality Usually a Lewis corrosive catalyst, for example, B(OR) 3 Another issue with AA’s This doesn’t happen in nature Easy to frame 6 membered ring instead of peptide Acid enactment can give the same item

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With 20 amino acids  confusion! How would we control response to couple 2 AAs together specifically & in the right arrangement? & at room temp (in vivo)? Organic frameworks & manufactured systems utilize security & actuation techniques! For peptide security arrangement Many distinctive R bunches on amino acids  potential for some side responses i.e.,

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Nature utilizes insurance & enactment as a component of its system to make proteins on the ribosome:

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Nature utilizes an Ester to actuate corrosive (protein blend): Adenylation

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Each AA is connected to its particular tRNA

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A particular sample: tyrosyl-tRNA synthase (from tyr)

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Control! Best way to guarantee specificity is to situate craved nucleophile (i.e., CO 2 - ) contiguous longing electrophile (i.e., P) What about Nonribosomal Peptide Synthase (NRPS)? Utilizes thioesters

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once more, we see selectivity in peptide bond arrangement As in the ribosome, the NRPS can situate the responding focuses in close nearness to one another, while physically blocking different destinations

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Chemical Synthesis of Peptides Synthesis of peptides is of awesome significance to science & science Why incorporate peptides? Study natural capacities (go about as hormones, neurotransmitters, anti-microbials, anticancer operators, and so forth) Study power, selectivity, steadiness, and so on. Auxiliary expectation Three-dimensional structure of peptides (utilization of NMR, and so on.) How? Arrangement combination Solid Phase blend Both utilization same actuation & assurance methodology

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e.g. isopenicillin N: To study compound IPNS, we have to orchestrate tripeptide (ACV) Small particle → use arrangement method Synthesis (in sol n ) can be long & low yielding But, can even now create enough for study

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Plan for Synthesis:

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Protection of Carboxylic corrosive: Selective Protection of R gathering (thiol):

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Both the amino gathering & carboxylate of cysteine need to couple to another AA But, we can’t respond every one of the 3 peptides without a moment's delay (must be stepwise)  we secure the amino gathering incidentally, then deprotect later Protection of the Amine: (BOC) 2 O = an anhydride

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Now that we have our ensured AA’s, we have to enact the carboxylate towards coupling Activation & Coupling (see exp 6): DCC = d i c yclohexyl c arbodiimide = Coupling reagent that