Photodecarboxylation of N-Adamantyl- and N-Phenylphthalimide Dipeptide Derivatives

Abstract

Abstract. New dipeptide derivatives 1 and 3 were synthesized and their reactivity in the photochemical reaction of decarboxylation was investigated. The photodecarboxylation of N-adamantyl derivatives 1a and 1b and N-phenylphthalimide derivatives 3a and 3b probably takes place from the triplet excited state. The triplet excited state of 1a, 3a and 3b was characterized by laser flash photolysis. N-phenylphthalimides 3a and 3b undergo 2−5 times more efficient photodecarboxylation than N-adamantylphthalimides 1a and 1b. The aminoacid residue (Phe or Gly) at the C-terminus of the dipeptide does not influence the photodecarboxylation efficiency. Product selectivity in the photoreactions is determined by the conformation of the molecules. N-phenylphthalimides with the separated electron donor (carboxylate) and acceptor moiety (phthalimide) give only simple decarboxylation products, whereas N-adamantyl derivatives also give cyclization products.

Photocyclization of Tetra- and Pentapeptides Containing Adamantylphthalimide and Phenylalanines: Reaction Efficiency and Diastereoselectivity

“…To synthesize the target molecules, the carboxylic acid in dipeptide 21 was activated by HBTU and treated with Bn-protected peptides 27 , 29 , and 31 . The Bn group was cleaved off, as shown in the example of pentapeptide 32 in Scheme , by use of Et 3 SiH and Pd/C, which was found as a protocol compatible with the phthalimide group …”

“…For the HRMS analyses, the samples were analyzed in a positive mode applying nanoUPLC-ESI-qTOF on instruments. The known precursors, 2-{[3-( N -phthalimido)­adamantan-1-yl]­carboxamido}­acetic acid ( 21 ) and benzyl-2-{[3-( N -phthalimido)­adamantan-1-yl]­carboxamido}­acetate ( 19 ), were prepared according to the literature precedent …”

“…16 Furthermore, Mariano et al proposed that the efficiency of the photocyclization depended on the relative stabilities and equilibration of the peptide intrastrand electron transfer states. 17 We have become interested in the photoinduced phthalimide-promoted preparation of polycyclic molecules 18−20 and peptide cyclizations 21 and found that photocyclization of adamantane dipeptides proceeds enantioselectively with a memory of chirality. 22 However, when we tried to expand the use of the photodecarboxylation protocol to peptides containing tyrosine at the peptide C-terminus, we found that the photodecarboxylation did not take place.…”

[3 + 2] Cycloaddition with photogenerated azomethine ylides in β-cyclodextrin

“…We found out that H-abstraction reactions were about ten times more efficient in the β-CD complexes than in the isotropic solution, and the macrocyclic host affected the stereochemistry of the reaction. Moreover, we studied photodecarboxylation reactions initiated by the phthalimide chromophore [17][18][19] and applied them in cyclizations with memory of chirality [20] and diastereoselective peptide cyclizations [21]. Photodecarboxylations were also intensively investigated in a series of nonsteroidal anti-inflammatory drugs [22][23][24] such as ketoprofen [25][26][27][28][29][30][31][32][33][34], due to photoallergic responses initiated by photodecarboxylation of these drugs [35].…”

Photophysical properties and electron transfer photochemical reactivity of substituted phthalimides

“…33 Photoinduced decarboxylation is also important in the context of different photocatalytic processes. [34][35][36][37][38][39][40][41] We have become interested in photodecarboxylation reactions initiated by phthalimide chromophore [42][43][44] and applied them in cyclizations with memory of chirality 45 and diastereoselective peptide cyclizations. 46 Furthermore, the photodecarboxylation efficiency was investigated in a series of phthalimide derivatives of adamantane amino acids, where we modified the distance between the electron donor (carboxylate) and the acceptor (phthalimide).…”