Simple and Stereocontrolled Preparation of Benzoylated Phenylalanine Using Friedel–Crafts Reaction in Trifluoromethanesulfonic Acid for Photoaffinity Labeling

The Life of Pi Star: Exploring the Exciting and Forbidden Worlds of the Benzophenone Photophore

“…Han et al developed another sterically restricted amino acid (3-(3′-fluorenyl-9′-oxo)- l -alanine, 283 ) (Figure ). Hashimoto et al synthesized a doubly labeled amino acid containing a BP and a trifluoromethyl-diazirine photolabile moiety ( 284 ). Both photophores can be excited at 350 nm; however, there are a fast photophore (diazirine) and a slow photophore (BP), which might allow unique labeling particularly in protein–protein interactions.…”

“…Pretubulysin (307), a biosynthetic precursor of tubulysin, possesses a high tubulin-degradation activity. Eirich et al synthesized the clickable, photoactivatable ABP of pretubulysin (308, Figure 174).…”

Utilization of Acidic α-Amino Acids as Acyl Donors: An Effective Stereo-Controllable Synthesis of Aryl-Keto α-Amino Acids and Their Derivatives

“…For convenient synthesis of benzophenone-based α -amino acid derivatives, we carried out Friedel-Crafts acylation between phenylalanine derivatives 92a-b and diazirinylbenzoyl chloride 95 in the presence of TfOH [81]. Furthermore, two photophore (benzophenone and diazirine) based structures ( 97 ) were prepared as an interesting study and their detailed analysis of photo-irradiation were also investigated, which may contribute to the investigation of peptide-receptor interactions in photoaffinity labeling (Scheme 17).…”

Friedel–Crafts reactions for biomolecular chemistry

“…Potentially relevant reactions to the proposed chemical evolution reaction are shown at the bottom: (i) reaction of indole and pyruvate analogues (oxygen-substituted α,β-unsaturated carbonyl compounds), 120 (ii) tautomerization of pyruvate forming hydroxy-substituted α,β-unsaturated carboxylic acid as an enol form, and (iii) chemical structure of phosphoenolpyruvate (α,β-unsaturated carbonyl compound with a substitution on the oxygen of the enol unit) that is a known intermediate for modern glycolysis 121 as well as a possible species in the prebiotic time. 122 (C) Reaction of phenylalanine and benzoyl chloride forming benzophenone-substituted unnatural amino acid 126 that is useful for the identification of interactions between biomolecules in cellular systems through irradiation of ultraviolet light ( photo-crosslinking). 124 (D) Acetylation of tyrosine with acetyl chloride forming acetyltyrosine as an intermediate for the chemical synthesis of 3,4-dihydroxyphenylalanine (DOPA).…”

“…S18, ESI †). 126 The use of an extremely strong acid (trifluoromethanesulfonic acid or triflic acid, pK a < −14) is plausibly necessary in order to fully suppress the reactivity of the amine group through protonation.…”