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.
-Based on information in the passage, which amine was most likely proposed as a replacement for piperidine in Scheme III?

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.
-Based on information in the passage, which amine was most likely proposed as a replacement for piperidine in Scheme III?

Quizplus · Accepted Answer

11ecba2d_12a8_ce3d_a3bf_0d18997f35a7_MD0008_00 Amines can be classified as primary, secondary, tertiary, or quaternary (ie, one, two, three, or four non-hydrogen substituents, respectively). The passage states that piperidine is a heterocyclic secondary (2°) amine that is typically used to remove the Fmoc protecting group. Heterocyclic molecules are ring structures that contain at least one heteroatom (neither carbon nor hydrogen) within the ring. Secondary amines are nitrogen atoms bound to two carbon atoms (alkyl and/or aryl groups). An alternative to piperidine was explored because the use of piperidine is regulated. An amine that is structurally similar to piperidine (ie, a heterocyclic 2° amine) would most likely be the best alternative. Pyrrolidine, shown in Choice D, is the only amine given that is both heterocyclic and a 2° amine. (Choice A) This is a secondary amine but, it is not heterocyclic because the nitrogen atom is not part of the ring. (Choice B) This is an aromatic amine. It contains three carbon-nitrogen bonds, so it is not a secondary amine. (Choice C) This amine is heterocyclic, but it is a 3° amine rather than a 2° amine. Educational objective: Amines can be classified as primary, secondary, tertiary, or quaternary (ie, one, two, three, or four non-hydrogen substituents, respectively).

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