Rapid approach to 3,5-disubstituted 1,4-benzodiazepines via the photo-fries rearrangement of anilides.
Different anilides derived from carboxylic acids and substituted anilines have been submitted to the photochemically induced Fries rearrangement giving the corresponding o-amino phenones under conditions that are compatible with the presence of acid-labile groups (such as N-Boc or TBDMSO) on R1 and R3. These compounds, not easily obtained in other ways, are useful building blocks for the preparation of benzocondensated heterocycles. After coupling with N-Boc amino acids and TFA-mediated deprotection, the products cyclized to the corresponding 3,5-disubstituted 1,4-benzodiazepin-2-ones, privileged structures predominantly active in the central nervous system. The same results were obtained by coupling with N-Cbz-protected alpha-amino acids followed by microwave assisted hydrogenolysis. When the Fries rearrangement was carried out on the anilide derived from N-Boc-Ala-OH and the further coupling done with N-Cbz-(OMe)Asp-OH, the formed benzodiazepines could be inserted in a peptide chain for the preparation of conformationally constrained peptidomimetics.
Ferrini
Serena
S
Dipartimento di Chimica and Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, Via A. Moro, 53100 Siena, Italy. taddei.m@unisi.it
Ponticelli
Fabio
F
Taddei
Maurizio
M