Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• , the authors found a high diastereoselectivity in the Ugi-4CR conducted with a carbonyl linked at C-17, a sterically crowed position very close to the axial methyl group placed of C-13. This step was implemented as part of the synthetic route toward steroidal 2,5-diketopiperazine 6, based on a strategy

• protocol provided a small library of steroidal 2,5-diketopiperazines 6 obtained as a single diastereomer, thus proving the high diastereoselection of the initial Ugi-4CR with the steroidal carbonyl substrate. In the 2,5-diketopiperazine ring, the configuration of the new asymmetric center C-3’ was S, a

• result confirmed by NOESY experiments. In comparison with the work described above, it can be suggested that in the case of the 2,5-diketopiperazine synthesis, the distance of the carbonyl moiety to the steroidal nucleus is determinant for the diastereoselection of the Ugi-type reaction. Thus, when the

Sequential Ugi reaction/base-induced ring closing/IAAC protocol toward triazolobenzodiazepine-fused diketopiperazines and hydantoins

• Robby Vroemans,
• Fante Bamba,
• Jonas Winters,
• Joice Thomas,
• Jeroen Jacobs,
• Luc Van Meervelt,
• Jubi John and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 626–633, doi:10.3762/bjoc.14.49

• together all necessary functionalities for further transformations. The Ugi adducts were then subjected to a base-induced ring closing and an intramolecular azide–alkyne cycloaddition reaction in succession to obtain highly fused benzodiazepine frameworks. Keywords: benzodiazepine; 2,5-diketopiperazine

• multiring-fused derivatives incorporating all these heterocyclic moieties. We hypothesized that 2,5-diketopiperazine-fused triazolobenzodiazepine could be obtained by proper functionalization of building blocks starting with an Ugi reaction; followed by two ring-closing steps, one being a base-induced

• 2,5-diketopiperazine ring C. On the other hand, in the case of Ugi adduct D, a base induced intramolecular nucleophilic attack of the amide N-atom to the carbonyl carbon occurs (in intermediate E) and the hydantoin ring F forms by the elimination of the trichloromethyl anion. Conclusion In conclusion

Three-component synthesis of highly functionalized aziridines containing a peptide side chain and their one-step transformation into β-functionalized α-ketoamides

• Lena Huck,
• Juan F. González,
• Elena de la Cuesta and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2016, 12, 1772–1777, doi:10.3762/bjoc.12.166

• -piperazinediones and involving a one-pot sequence of reactions achieving regioselective opening of the 2,5-diketopiperazine ring and diastereoselective generation of an aziridine ring. This method allows the preparation of N-unprotected, trisubstituted aziridines bearing a peptide side chain under mild conditions

The diketopiperazine-fused tetrahydro-β-carboline scaffold as a model peptidomimetic with an unusual α-turn secondary structure

• Francesco Airaghi,
• Andrea Fiorati,
• Giordano Lesma,
• Manuele Musolino,
• Alessandro Sacchetti and
• Alessandra Silvani

Beilstein J. Org. Chem. 2013, 9, 147–154, doi:10.3762/bjoc.9.17

• ]. Moreover, recently some tetracyclic β-carbolines have been described to act as selective inhibitors in the anticancer field [8][9], or to be endowed with antimalarial properties [10]. 2,5-Diketopiperazine (DKP)-based compounds are heterocyclic scaffolds structurally similar to peptides. They have attracted