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Photochemistry of phthalimidoadamantane dipeptides: effect of amino acid side chain on photocyclization

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Abstract

A series of dipeptides 1 was synthesized that at the N-site contained 3-(N-phthalimidoadamantane-1-carboxylic acid and at the C-site different aliphatic or aromatic l- or d-amino acids. The photochemical reaction of dipeptides 1 under acetone-sensitized conditions gave simple decarboxylation products 6, and decarboxylation-induced cyclization products 7, as well as some secondary products 8 and 9 formed by elimination of H2O or ring enlargement, respectively. Molecules 9 undergo secondary photoinduced H-abstractions by the phthalimide chromophore, delivering more complex polycycles 11. The photodecarboxylation-induced cyclization to 7 was observed only with phenylalanine (Phe), proline (Pro), leucine (Leu) and isoleucine (Ile). Contrary to dipeptides with Phe, the cyclization takes place with almost complete racemization at the amino acid chiral center, but diastereoselectively giving only one pair of enantiomers. The conducted investigation is important as it provides the breath and the scope of dipeptide cyclizations activated by phthalimides.

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Scheme 1
Scheme 2
Scheme 3
Fig. 1

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On request from the authors or via a website: https://mojoblak.irb.hr/s/PXPWDXZ2QCp3daC. Samples are available from the authors on request.

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Funding

This research was funded by the Croatian Science Foundation (HRZZ grants no. HRZZ IP-2014-09-6312 and HRZZ-IP-2019-04-8008).

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Author notes

  1. Irena Sović

    Present address: Selvita Ltd., Prilaz Baruna Filipovića 29, 10000, Zagreb, Croatia

  2. Zlatan Spahić

    Present address: Faculty of Science, University of Zagreb, Horvatovac 102 A, 10000, Zagreb, Croatia

Authors and Affiliations

  1. Department of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička Cesta 54, 10000, Zagreb, Croatia

    Margareta Sohora, Irena Sović, Zlatan Spahić, Darko Kontrec & Mladenka Jurin

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  1. Margareta Sohora
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Correspondence to Margareta Sohora.

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Supplementary Information

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43630_2023_430_MOESM1_ESM.pdf

Supplementary file1 (PDF 11597 KB) Synthetic procedures and selected photochemical experiments, HPLC chromatograms on chiral stationary phases, computational data and copies of 1H and 13C NMR spectra.

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Sohora, M., Sović, I., Spahić, Z. et al. Photochemistry of phthalimidoadamantane dipeptides: effect of amino acid side chain on photocyclization. Photochem Photobiol Sci 22, 2071–2080 (2023). https://doi.org/10.1007/s43630-023-00430-4

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