Photochemical Activation of Amino Acids: From the Synthesis of Enantiomerically Pure β,γ‐Unsaturated Amino Acids to Macrocyclic Ring Systems

Abstract

Amino acids whose amino groups are transformed into phthalimido chromophores are versatile substrates for photochemical transformations such as cyclization, isomerization, and P-cleavage. These processes are initiated by homolytic or mesolytic CH activation and depend on the spin state of the excited substrate. Derivatives of a-amino acids without strong electron-donating substituents [Abu, Nva, Val, Leu, Ile, Tle, Phe, Met(SO)] react by initial homolytic CH activation and solely via their first excited singlet states, whereas substrates with strong electron-donating substituents (Tyr, DOPA, Met, Glu, Asp) react by initial photoinduced electron transfer (PET) followed by mesolytic CH activation and solely via their first excited triplet states. The S-alkyl cysteine derivatives are the only ones which show competing singlet and triplet state reactivity with pronounced spin-determined regioselective CH activation. The amino dicarboxylic acids Glu and Asp could be applied as the carboxylates in PET reactions, a strategy which also opened up a new synthetic approach to medium-and large-ring systems.

Photochemistry of three N‐acetoacetyl amino acid methyl esters: structure elucidation of the radiation products by gas chromatography/mass spectrometry

“…Process (1) corresponds to the loss of ketene from 3 and (2) represents an analogous H-transfer via a sixmembered transition state. Both result in the loss of the entire acyl group, whereas (3) leads to the loss of and an enol is formed which would not be CH 2 CO, expected to fragment by a further loss of The CH 2 CO. J.…”

“…In a long-term research project, we are investigating the photochemical behavior of N-and C-activated amino acids and peptide model substrates. 1,2 The background of these studies is the understanding of energy and electron transfer processes in oligopeptides. In order to correlate short-and long-distance processes with the properties of the excited part of molecule, we have been systematically investigating model compounds with restricted reactive sites.…”

Photoinduced decarboxylation reactions

“…Covalently linked chromophores which show highly selective photochemistry include aromatic ketones (C-terminal), 1 pyruvamides (N-terminal) 2 and especially the phthalimide group. 3 The advantages of all these chromophores were as follows: absorption in the 310-350 nm region, rapid intersystem crossing (ISC) to give relatively long-lived triplet excited states, selective activation of proximate C-H bonds (for aromatic ketones or pyruvamides) or photoinduced electron-transfer activity (for phthalimides). An especially attractive photochemical reaction was discovered when C-unprotected w-phthalimido carboxylic acids were irradiated.…”

Photoinduced homolytic C–H activation inN-(4-homoadamantyl)phthalimide

“…Furthermore, suitably substituted phthalimides deactivate from the excited state by intramolecular H-abstractions to yield cyclization products, often benzazepinone derivatives [ 35 – 37 ]. Therefore, photoinduced homolytic C–H activation by phthalimide derivatives can, in principle, be used in organic synthesis for the preparation of benzazepinones [ 21 , 25 , 33 ].…”