An in-depth exploration of six decades of the Kröhnke pyridine synthesis - a review.

The Kröhnke Pyridine Synthesis has been discovered about six decades ago (1961), by Fritz Kröhnke and Wilfried Zecher at the University of Giessen. The original method involved the reaction of α-pyridinium methyl ketone salts with α,ß-unsaturated carbonyl compounds in the presence of a nitrogen source, frequently ammonium acetate. Since its discovery, the Kröhnke methodology has been demonstrated to be suitable for the preparation of mono-, di-, tri- and tetra-pyridines, with important applications in several research fields. Over the years, a number of modifications to the original approach have been developed and reported, enabling for the broad applicability of these methods even in modern days, also for the synthesis of non-pyridine compounds. In this critical and tutorial review, we will thoroughly explore and discuss the potential of the original method, the refinements that have been made over the years, as well as some applications arising from each type of pyridine and/or non-pyridine compounds produced by Kröhnke's approach.

Recent Advances in Fluorescent Theranostics for Alzheimer's Disease: A Comprehensive Survey on Design, Synthesis, and Properties.

Alzheimer's disease (AD) is the most common form of neurodegenerative dementia that is rapidly becoming a major health problem, especially in developed countries because of their increasing life expectancy. Two main problems are often associated with the disease: (i) the absence of a widely accessible "gold-standard" for early diagnosis and (ii) lack of effective therapies with disease-modifying effects. The recent success of the monoclonal antibody lecanemab played an important role not only in clarifying a possible druggable pathway but also in spelling the revival of small molecule drug discovery. Unlike bulky biologics, small molecules are structurally less complex, generally cheaper, and compatible with at-home oral consumption, making it feasible for people to start their drug regimen early and stay on it longer. In this sense, small-molecule near-infrared fluorescent theranostics have been gaining more and more attention from the scientific community, as they have the potential to simultaneously provide diagnostic outputs and deliver therapeutic action, paving the way toward personalized medicine in AD patients. They also have the potential to shift the diagnostic "status-quo" from expensive and limited-access PET radiotracers toward inexpensive and handy imaging tools widely available for primary patient screening and preclinical animal studies. Herein, we review the most recent advances in the field of fluorescent theranostics for Alzheimer's disease, detailing their design strategies, synthetic approaches and imaging and therapeutic properties in vitro and in vivo. With this Review, we intend to provide a milestone in the acquired knowledge in the field of AD theranostics, encouraging the future development of properly designed theranostic compounds with improved chances to reach clinical applications.