Química Orgánica 2 · Aminoácidos y conectividad de los péptidos
ATZ-glycine and alanine from Edman degradation of Gly-Ala
Condiciones: PhNCS, pH 9; then TFA
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El mecanismo, paso a paso
Siguiente reproduce las flechas curvas de cada paso y las explica. Los pasos escritos están abajo.
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The N-terminal amine adds to PhNCS
At pH 9 the N-terminal amine is unprotonated and nucleophilic. It attacks the central carbon of phenyl isothiocyanate, and the C=N π pair moves onto the aryl nitrogen.
Las flechas curvas
- The amine lone pair attacks the isothiocyanate carbon.
- The C=N π pair moves onto the aryl nitrogen.
Water protonates the anilide nitrogen
The negatively charged aryl nitrogen takes a proton from water, the proton relay in the buffered solution.
Las flechas curvas
- The nitrogen lone pair takes a proton from water.
- The O–H pair stays on oxygen as hydroxide.
Hydroxide removes the N–H proton
Hydroxide removes a proton from the positively charged nitrogen, giving the neutral phenylthiourea of the peptide.
Las flechas curvas
- A hydroxide lone pair takes the N–H proton.
- The N–H pair stays on nitrogen.
TFA protonates the amide carbonyl
After the buffer is removed, anhydrous TFA protonates the first amide carbonyl, making it electrophilic toward the nearby thiourea sulfur.
Las flechas curvas
- The amide oxygen lone pair takes the TFA proton.
- The O–H pair stays on oxygen as trifluoroacetate.
Sulfur attacks the amide carbon
The thiocarbonyl sulfur is five atoms from the amide carbon, so it closes a five-membered ring by attacking the protonated carbonyl carbon.
Las flechas curvas
- A sulfur lone pair attacks the protonated amide carbon.
- The C=O+ π pair moves onto oxygen, giving an OH group.
Deprotonate the ring nitrogen
Trifluoroacetate removes the N–H proton of the former N-terminus; that pair forms a C=N bond and the C=S+ π pair returns to sulfur, giving a neutral thiazoline.
Las flechas curvas
- A trifluoroacetate lone pair takes the N–H proton.
- The N–H pair forms the C=N π bond.
- The C=S+ π pair moves onto sulfur.
Protonate the alanine nitrogen
A second TFA protonates the amide-derived nitrogen, now sp3 and basic, so alanine can leave as a neutral amine.
Las flechas curvas
- The nitrogen lone pair takes the TFA proton.
- The O–H pair stays on oxygen.
Why only the first residue
Ring size decides.
Alanine leaves
The OH lone pair re-forms a C=O bond and expels the alanine nitrogen as a neutral amine, giving the protonated thiazolinone.
Las flechas curvas
- An oxygen lone pair forms the C=O π bond.
- The C–N pair stays on nitrogen as the amine lone pair.
Deprotonate the thiazolinone
Trifluoroacetate removes the proton from the carbonyl oxygen, giving the neutral anilinothiazolinone (ATZ).
Las flechas curvas
- A trifluoroacetate lone pair takes the O–H proton.
- The O–H pair stays on the carbonyl oxygen.
TFA protonates alanine
In TFA the released alanine amine is protonated.
Las flechas curvas
- The amine lone pair takes the TFA proton.
- The O–H pair stays on oxygen.
ATZ-glycine and alanine
The products are the anilinothiazolinone of glycine, extracted and converted in aqueous acid to the stable PTH-glycine for identification, and alanine (as its trifluoroacetate) with its stereocentre unchanged; on a longer peptide this alanine would be the new N-terminus.
Qué vas a practicar
Draw Edman degradation of Gly-Ala: phenylthiourea formation at the N-terminus, then TFA-promoted cyclization that releases alanine and the anilinothiazolinone of glycine.
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