Passage
The N-terminus of an amino acid must be protected with 9-fluorenylmethoxycarbonyl (Fmoc) during solid state peptide synthesis to avoid side reactions (Scheme I) .
Scheme IThe Fmoc protecting group is typically removed with piperidine (Scheme II) , a heterocyclic secondary amine.
Scheme IIBecause the use of piperidine is restricted, structurally similar amines were examined as possible replacements. To determine whether piperidine analogues were suitable alternatives for Fmoc removal, deprotection of Compound 2 was carried out with several amine bases (Scheme III) .
Scheme IIICompound 2 was prepared from L-tryptophan and Fmoc-Cl, and the reaction was monitored by thin-layer chromatography (TLC) and visualized by ultraviolet light. The deprotections were done with piperidine and each analogue using a microwave set to 155 watts at 75 °C for 15 seconds. The products of the deprotections were analyzed by high-performance liquid chromatography (HPLC) and mass spectrometry; the retention times of the products were compared to tryptophan and Compound 2 standards.
Adapted from O.P. Luna et al, "Deprotection Reagents in Fmoc Solid Phase Peptide Synthesis: Moving Away from Piperidine?." Molecules. ©2016 MDPI.
-Which reaction would best give data to support the need of a cyclic amine for removal of the Fmoc group?

Question

Passage
The N-terminus of an amino acid must be protected with 9-fluorenylmethoxycarbonyl (Fmoc) during solid state peptide synthesis to avoid side reactions (Scheme I) .

Scheme IThe Fmoc protecting group is typically removed with piperidine (Scheme II) , a heterocyclic secondary amine.

Scheme IIBecause the use of piperidine is restricted, structurally similar amines were examined as possible replacements. To determine whether piperidine analogues were suitable alternatives for Fmoc removal, deprotection of Compound 2 was carried out with several amine bases (Scheme III) .

Scheme IIICompound 2 was prepared from L-tryptophan and Fmoc-Cl, and the reaction was monitored by thin-layer chromatography (TLC) and visualized by ultraviolet light. The deprotections were done with piperidine and each analogue using a microwave set to 155 watts at 75 °C for 15 seconds. The products of the deprotections were analyzed by high-performance liquid chromatography (HPLC) and mass spectrometry; the retention times of the products were compared to tryptophan and Compound 2 standards.
Adapted from O.P. Luna et al, "Deprotection Reagents in Fmoc Solid Phase Peptide Synthesis: Moving Away from Piperidine?." Molecules. ©2016 MDPI.
-Which reaction would best give data to support the need of a cyclic amine for removal of the Fmoc group?

Quizplus · Accepted Answer

11ecba2d_12a9_1c5e_a3bf_059c50e2ba40_MD0008_00 Conclusions about a variable can be drawn from experimental data. To determine whether a result is dependent on a specific variable, the experiment is replicated and the variable in question is changed while all other variables are held constant so that only one parameter of the experiment is changed. Experimental setups in which more than one variable is changed cannot be compared to the original experiment because differences in the results cannot be attributed to any one variable. The passage states that piperidine, a heterocyclic secondary amine, is used to remove Fmoc, a protecting group. The two variables in the amine's structure are the substitution of the nitrogen atom (secondary) and whether the amine is cyclic. To conclude that the amine must be cyclic for Fmoc group removal, a noncyclic amine should be used for comparison. Therefore, researchers should react Compound 2 with a noncyclic secondary amine and determine whether the Fmoc group was removed. If the Fmoc group is removed by a noncyclic amine, the amine does not need to be cyclic for deprotection whereas if the Fmoc group is not removed, the cyclic nature of the amine is important for deprotection. (Choices A and B) Tryptophan does not contain an Fmoc group. Therefore, treating it with an amine would not contribute any data to support the conclusion that a cyclic amine is necessary for Fmoc removal. (Choice D) Using a tertiary noncyclic amine to attempt Fmoc group removal would not help support the conclusion that amines must be cyclic to remove Fmoc because both variables (cyclic nature and substitution) were changed. If Fmoc removal does not occur, it would be unclear whether it was because the amine is noncyclic or because the amine is tertiary, or both. Educational objective: Conclusions about a variable can be drawn from experimental data. To determine whether a result is dependent on a specific variable, the experiment is repeated and the variable in question is changed while all other variables are held constant so that only one parameter of the experiment changes.

Passage the N-Terminus of an Amino Acid Must Be Protected with with 9-Fluorenylmethoxycarbonyl