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Photoisomerizable peptides are promising drug candidates in photopharmacology. While azobenzene- and diarylethene-containing photoisomerizable peptides have already demonstrated their potential in this regard, reports on the use of spiropyrans to photoregulate bioactive peptides are still scarce. This work focuses on the design and synthesis of a spiropyran-derived amino acid, (S)-2-amino-3-(6'-methoxy-1',3',3'-trimethylspiro- [2H-1-benzopyran-2,2'-indolin-6-yl])propanoic acid, which is suitable for the preparation of photoisomerizable peptides. The utility of this amino acid is demonstrated by incorporating it into the backbone of BP100, a known membrane-active peptide, and by examining the photoregulation of the membrane perturbation by the spiropyran-containing peptides. The toxicity of the peptides (against the plant cell line BY-2), their bacteriotoxicity (E. coli), and actin-auxin oscillator modulation ability were shown to be significantly dependent on the photoisomeric state of the spiropyran unit. [ABSTRACT FROM AUTHOR]

A set of building blocks based on the 4,5,6,7‐tetrahydro‐pyrazolo[1,5‐a]pyrazine scaffold is synthesized in a multigram scale in a cost‐efficient manner. The possibility of the introduction of different substituents, neutral or functionalized in different positions of pyrazole and/or piperazine rings, is shown. The efficacy of using NH‐pyrazole carbonic acids as a key intermediate of the process is demonstrated. The regioselectivity for direct insertion of the substituent to the 4,5,6,7‐tetrahydro‐pyrazolo[1,5‐a]pyrazine core is discussed. The synthetic perspectives for using the functionalized 4,5,6,7‐tetrahydro‐pyrazolo[1,5‐a]pyrazine as a bifunctional scaffold is discussed. The utilizing of building blocks obtained for the different region‐ and/or stereoselective synthesis, including sole transformations or modifications of functional groups, is demonstrated. The advantages of the proposed approach are proven compared with the other known methodologies. [ABSTRACT FROM AUTHOR]

The electrochemical Shono oxidation of Boc‐protected cyclic amines was revised. The conditions for scalable electrochemical synthesis of cyclic enecarbamates were found. The developed protocol included recycling of the full range of used reagents, favoring to E‐factor reduction according to Green Chemistry requirements. The method opened the way for the convenient preparation of previously uncommon materials, which could become useful synthetic intermediates. Their synthetic potential was evaluated in [2+1] and [2+2] cycloadditions as well as electrophilic functionalization. Moreover, functionalized enecarbamates with carbonyl groups in β‐position were used as latent 1,3‐bielectrophiles in classical heterocyclizations. In a case of the hydrazine, the corresponding unusually decorated pyrazoles were prepared. The proposed methodology is a straightforward tool for the design and synthesis of Medicinal Chemistry relevant building blocks. As examples, 5‐fluoro pipecolic and 3‐fluoro isonipecotic acids were synthesized starting from Boc‐protected esters of the pipecolic and the isonipecotic acids respectively; the 5‐step approach to pyrazole containing α‐aminoacids with different linkers between the aminoacidic and pyrazole moieties was elaborated based on the cheapest commercially available racemic and chiral cyclic α‐aminoacids; the convenient approach to the functionalized tetrahydropyrido[3,4‐d]pyridazines was proposed starting from Boc‐protected ester of the isonipecotic acids. [ABSTRACT FROM AUTHOR]