Multicomponent reactions (MCRs) are fundamentally different from two-component reactions in several aspects. Among the MCRs, those with isocyanides have developed into popular organic-chemical reactions in the pharmaceutical industry for the preparation of compound libraries of low-molecular druglike compounds. With a small set of starting materials, very large libraries can be built up within a short time, which can then be used for research on medicinal substances. Due to the intensive research of the last few years, many new backbone types have become accessible. MCRs are also increasingly being employed in the total synthesis of natural products. MCRs and especially MCRs with isocyanides offer many opportunities to attain new reactions and basic structures. However, this requires that the chemist learns the “language” of MCRs, something that this review wishes to stimulate.

Multicomponent Reactions with Isocyanides.

Recent Developments in the Isonitrile‐Based Multicomponent Synthesis of Heterocycles

Recent Developments of Transition-State Analogue Glycosidase Inhibitors of Non-Natural Product Origin

Multicomponent reactions are one of the most interesting concepts in modern synthetic chemistry and, as shown in this critical review, they provide an attractive entry into pyrrole derivatives, which are very important heterocycles from many points of view including medicinal and pharmaceutical chemistry and materials science (97 references).

Multicomponent reactions for the synthesis of pyrroles

Catalyst-free reactions developed during the last decade and the latest developments in this emerging field are summarized with a focus on catalyst-free reactions in-water and on-water. Various named reactions, multi-component reactions and the synthesis of heterocyclic compounds are discussed including the use of various energy input systems such as microwave- and ultrasound irradiation, among others. Organic chemists and the practitioners of this art both in academia and industry hopefully will continue to design benign methodologies for organic synthesis in aqueous media under catalyst-free conditions by using alternative energy inputs based on fundamental principles.

Benign by design: catalyst-free in-water, on-water green chemical methodologies in organic synthesis

The aryldihydropyridines first prepared by Hantzsch almost 100 years ago have recently been found to be highly effective calcium antagonists with suitable pharmacological profiles. An illustrative example is dimethyl-l,4-dihydro-2,6-dimethyl-4-(o-nitrophenyl)pyridine-3,5-dicarboxylate (Nifedipine) which is already employed therapeutically. This substance lowers the frequency of attack of angina pectoris and reduces blood pressure. The discovery of the therapeutic activity of this class of substances initiated renewed investigation of the Hantzsch condensation and the synthesis of numerous 4-aryldihydropyridines and related compounds. Qualitative and quantitative structure/activity relationships of these substances can be deduced from their biological data.

4-Aryldihydropyridines, a New Class of Highly Active Calcium Antagonists

1,4-Dihydropyridines of the formula ##STR1## in which n is 0,1 or 2, and R1 to R7 can have a wide variety of meanings, which possess inotropic action, and many of which are new, are useful in increasing the influx of Ca++ into cells, particularly in combatting coronary and vascular diseases, hypertension swelling in the mucous membranes and diseases involving increased blood sugar or an incorrect salt and fluid balance.

Method of combatting coronary and vascular diseases

1,4-Dihydropyridines characterized by a carbo(arylalkoxy) group in the 5-position, an aryl group in the 4-position and a alkanoyl or carbalkoxy group in the 3-position and further optionally substituted in the 1,2 and 6-positions are coronary dilating, spasmolytic and hypotensive agents. The compounds, of which 2,6-dimethyl-3-carbomethoxy-4-(2-nitrophenyl)-5-carbobenzoxy-1,4-dihydropyridine is a representative embodiment, are prepared through the reaction of an ylidene-β-dicarbonyl compound, which may be generated in situ from the corresponding β-dicarbonyl compound and an aldehyde, and an enaminocarboxylic acid ester, which may also be generated in situ from a β-dicarbonyl compound and an amine.

1,4-dihydropyridines

Die von Hantzsch vor nahezu hundert Jahren synthetisierten Aryldihydropyridine erwiesen sich in jungerer Zeit als hochwirksame und gut vertragliche Calcium-Antagonisten Paradebeispiel ist der bereits therapeutisch angewandte 1,4-Dihydro-2,6-dimethyl-4-(o-nitrophenyl)pyridin-3,5-dicarbonsaure-dimethylester (Nifedipine) Dieser Stoff setzt die Anfallshaufigkeit bei Angina pectoris herab und senkt den Blutdruck Die Entdeckung der therapeutischen Wirksamkeit dieser Stoffklasse initiierte erneute Untersuchungen der Hantzsch-Kondensation sowie die Synthese zahlreicher 4-Aryldihydropyridine und verwandter Verbindungen Aus ihren biologischen Daten lassen sich qualitative und quantitative Struktur-Wirkungs-Beziehungen ableiten

4‐Aryldihydropyridine, eine neue Klasse hochwirksamer Calcium‐Antagonisten

1,4-Dihydropyridines characterized by alkyl groups in 2- and 6-positions, a pyridyl group in 4-position, a carboxylate in 5-position and an aminoalkyl carboxylate group in 3 position, demonstrate coronary vessel dilation and anti-hypertensive effects.

Horst Meyer

Papers

4-Aryldihydropyridines, a New Class of Highly Active Calcium Antagonists

Method of combatting coronary and vascular diseases

1,4-dihydropyridines

4‐Aryldihydropyridine, eine neue Klasse hochwirksamer Calcium‐Antagonisten

1,4-Dihydropyridine carboxylic acid esters