methyl (2S)-2-amino-6-(phenylmethoxycarbonylamino)hexanoate → (S)-methyl 6-benzyloxycarbonylamino-2-carbazol-9-yl-hexanoate

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The novel photoreactive carbazole (Cbz)-based monomers of formula I according to the invention can be prepared as depicted in Schemes 1-4 (depicted hereinafter just before the Claims) and described in detail in Examples 1-4. Thus, Scheme 1 depicts the multi-step synthesis of Compound 7, (S) 6-(4-benzoyl-benzoylamino)-2-carbazol-9-yl-hexanoic acid, the photoreactive carbazole (Cbz)-based oxidizable monomer of formula I wherein the oxidizable group is carbazole, the moiety of the chemically reactive group is OH, the linker Y is —HN—CO—, Y′ is absent, the photoreactive moiety is benzophenone, n is 4 and m is 0. Compound 7 was obtained as a white solid in 98% yield. As shown in Example 1 and Scheme 1, protected L-Lys(Z)—OMe (1) is reacted with 2,4-dimethoxytetrahydrofuran (DMTHF) to give (S)-methyl 6-benzyloxycarbonylamino-2-carbazol-9-yl-hexanoate (3), followed by the removal of the benzyloxycarbonyl protecting group with 10% Pd/C to give (S)-6-amino-2-carbazol-9-yl-hexanoic methyl ester (4), In order to obtain (S)-6-(4-benzoyl-benzoylamino)-2-carbazol-9-yl-hexanoic acid methyl ester (6), compound 4 is reacted with 4-benzoyl benzoic acid (5) either by method A, which involves reaction in the presence of carbonyldiimidazole (CDI), or by method B in the presence of PCl5. The desired monomer 7 was obtained by refluxing under methanolic KOH, followed by neutralization to pH 3-4. Scheme 2 and Example 2 and show the synthesis of the Compound 14, (S)-6-(4-azido-benzoylamino)-2-carbazol-9-yl-hexanoic acid, the monomer of formula I wherein the oxidizable group is carbazole, the moiety of the chemically reactive group is OH, the linker Y is —HN—CO—, Y′ is absent, the photoreactive moiety is 4-azido phenyl, n is 4 and m is 0, starting from 4-aminobenzoic acid and resulting in 88% yield of monomer 14. Scheme 3 and Example 3 describe the synthesis of Compound 20, (S)-4-(2-(4-azidobenzoyloxy)ethoxy)-2-(9H-carbazol-9-yl)-4-oxobutanoic acid, the monomer of formula I wherein the oxidizable group is carbazole, the moiety of chemically reactive group is OH, the linker Y is —CO—O—, Y′ is —O—CO—, the photoreactive moiety is 4-azido phenyl, n is 1 and m is 2, starting from H-Asp-O-benzyl. Scheme 4 and Example 4 show the synthesis of Compound 26, (S)-5-(2-(4-azidobenzoyloxy)ethoxy)-2-(9H-carbazol-9-yl)-5-oxopentanoic acid, the monomer of formula I wherein the oxidizable group is carbazole, the moiety of chemically reactive group is OH, the linker Y is —CO—O—, Y′ is —O—CO—, the photoreactive moiety is 4-azido phenyl, n is 2 and m is 2, starting from H-Glu-O-benzyl. Other compounds of formula I can be obtained in similar manner starting from the appropriate starting compounds.

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