Alkene carboamination/oxidative denitrogenation of 3-allyl-3-hydrazinylindolin-2-ones: one-pot entry to spirocyclopropyloxindoles.

A one-pot protocol, consisting of a Pd-catalysed carboamination reaction, followed by -deprotection and oxidative denitrogenation, has been developed for the synthesis of diversely substituted spirocyclopropyloxindoles, in yields up to 73% and with diastereoselectivity close to 1 : 1. Readily accessible starting materials, mild reaction conditions, an easy to operate one-pot procedure and good functional group tolerance make this transformation a versatile tool for the synthesis of substituted spirocyclopropyloxindoles. This protocol successfully works on the gram-scale and allows access to both diastereoisomers separately.

Computational Design, Synthesis, and Biological Evaluation of Diimidazole Analogues Endowed with Dual PCSK9/HMG-CoAR-Inhibiting Activity.

Proprotein convertase subtilisin/kexin 9 (PCSK9) is responsible for the degradation of the hepatic low-density lipoprotein receptor (LDLR), which regulates circulating cholesterol levels. Consequently, the PCSK9 inhibition is a valuable therapeutic approach for the treatment of hypercholesterolemia and cardiovascular diseases. In our studies, we discovered , a polyimidazole derivative reducing the protein-protein interaction between PCSK9 and LDLR with an IC of 1.

Computational Design, Synthesis, and Biophysical Evaluation of β-Amido Boronic Acids as SARS-CoV-2 M Inhibitors.

The COVID-19 pandemic has given a strong impetus to the search for antivirals active on SARS-associated coronaviruses. Over these years, numerous vaccines have been developed and many of these are effective and clinically available. Similarly, small molecules and monoclonal antibodies have also been approved by the FDA and EMA for the treatment of SARS-CoV-2 infection in patients who could develop the severe form of COVID-19.

Enantiopure β-isocyano-boronic esters: synthesis and exploitation in isocyanide-based multicomponent reactions.

Various boron-containing isocyanides have been efficiently synthesized from the corresponding enantiopure β-substituted β-amino boronic acid pinacol esters, without need for protecting group interconversion, through a two-step, purification-free procedure. They were employed in a variety of isocyanide-based multicomponent reactions, proving to be reliable components for all of them and allowing the efficient synthesis of unprecedented, boron-containing peptidomimetics and heteroatom-rich small molecules, including biologically relevant cyclic boronates. Jointing together the β-amido boronic acid moiety, deriving from the isocyanide component, with prominent pharmacophoric rings emerging from the multicomponent process, a successful application of the molecular hybridization concept could be realized.

Unexpected chiral vicinal tetrasubstituted diamines via borylcopper-mediated homocoupling of isatin imines.

Addressing the asymmetric synthesis of oxindole-based α-aminoboronic acids, instead of the expected products we disclosed the efficient homocoupling of oxindole-based --butanesulfinyl imines, with the generation of chiral, quaternary 1,2-diamines in a mild and completely stereoselective way. The obtained 3,3'-bisoxindole derivatives were fully characterized by NMR and single-crystal X-ray diffraction analysis and proved to be single diastereoisomers and atropisomers. A plausible mechanism for the one-pot Cu(II)-catalyzed Bpin addition to the isatin-derived ketimine substrate and subsequent homocoupling is described.

Highly diastereoselective entry to chiral oxindole-based β-amino boronic acids and spiro derivatives.

We here describe the first Cu-catalysed, diastereoselective 1,2-addition of 1,1-diborylmethane to chiral ketimines for the synthesis of quaternary stereocenters and spiro compounds. The method provides easy access to a range of chiral, highly functionalized compounds, namely oxindole-based β,β'-disubstituted β-amino boronates, boron-containing peptidomimetics and six-, seven-membered spirocyclic hemiboronic esters. Such unprecedented compounds are mostly obtained in high yields and easily isolated as single diastereoisomers, paving the way to a more intense exploitation of boron-containing compounds in diversity-oriented chemistry and drug-discovery programs.

Allylation of isatin-derived N-Boc-hydrazones followed by Pd-catalyzed carboamination reaction: an entry to 3-spiro-pyrazolidyl-oxindoles.

The indium-mediated allylation of novel 3-(2-Boc-hydrazono)indolin-2-one derivatives, followed by a palladium-catalysed carboamination reaction, is described to afford unprecedented spirocyclic oxindoles in good yields. The method provides an efficient access to both and diastereoisomers of highly functionalized compounds, bearing an N-Boc, 5-substituted pyrazolidine ring at the C3-oxindole spiro junction. The versatility of the method is fully demonstrated starting from a series of substituted isatins and employing a variety of aryl halides in the key cyclization step.

Improved sperm count and motility in young men surgically treated for cryptorchidism in the first year of life.

Introduction: The timing of surgery in cryptorchidism has been debated for a long time. Reports on histology suggest better fertility outcomes with early surgery, whereas evidence of long-term improved fertility still lacks sound data. The aim of this study is to analyze sperm count and motility in a cohort of young men operated on during the first 2 years of life for cryptorchidism.