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Abstract

During the last decade we have witnessed the emergence of combinatorial chemistry as a tool for the discovery of new lead compounds. [1] Outstanding examples of sophisticated directed libraries have been reported, including pharmacophoric scaffolds, [2] bioactive metabolites, [2] designed ™unnatu-ral∫, diversity-oriented, pharmacophore-like, rigid, and versatile structures, [3] and even natural products with highly complex architectures. [4] The state-of-the-art in this field combines three main features: 1) suitably functionalized druglike ™privileged structures∫ [5] having specific spatial architecture and rigidity, 2) short synthetic pathways comprising reliable, clean, and high-yielding reactions, and 3) an overall ™diversification strategy∫ resulting ideally in ™libraries of libraries∫ [6] of scaffolds resembling evolution-selected molecules like natural products or drugs.Libraries are mainly based on a core molecule that is subjected to functional group manipulation which leads to a number of derivatives with the same central structure. Several versatile molecules that were key intermediates used by traditional medicinal chemists, for example, Corey©s lactone, the Wieland±Miescher ketone, and the Prelog±Djerassi lactone, could lead to a variety of apparently unrelated pharmacophoric frameworks. These starting materials are small molecules equipped with many reactive sites and functionalities, which can undergo both skeletal rearrangements and functional group interconversions. The use of such a polymorphic compound as the cornerstone of a library would be of great advantage since: 1) Many known synthetic key intermediates lead to medicinally important or ™privi-leged∫ scaffolds; 2) they possess high potential for both structural and functional diversification; 3) their chemical transformations and modifications in solution are well documented; and 4) the pharmacological activity of their descending structures is well precedented.To demonstrate the above concept, 2H-pyran-3(6H)-one (1) [7,8] was selected from among several synthetic key intermediates listed in the literature. As shown in Figure 1, derivatives of pyranone 1 exhibit significant biological activities, including antibacterial, antifungal, anticoccidial, antiinflamatory, and anticancer properties. Besides serving as intermediates in several natural product syntheses, such ZUSCHRIFTEN

Elektroorganische Synthese an der festen Phase mit Polymerkügelchen als Trägermaterial

“…Unser Zielmolekül war das hochfunktionalisierte 12 , das als Gerüstmolekül für weitere Diversifizierungen dienen kann (Schema ) 8g,h. 12 Das einfach silylgeschützte Diol 8 wurde durch Veresterung an das Polymerharz 3 b gebunden. Nach Entschützen mit Bu 4 NF wurde das Furan 9 wie oben beschrieben elektrolysiert.…”

Electroorganic Synthesis of 2,5-Dialkoxydihydrofurans and Pyridazines on Solid Phase Using Polymer Beads as Supports

“…Parallel to our work, the groups of Couladouros 27 and Schreiber 28 published a non-electrochemical method for the oxidation of furans using N-bromosuccinimide (NBS) and very interesting strategies for the diversification of the reaction products. When we applied the NBS-oxidation method for polymer bound substrate 7 we isolated reaction product 9 in 30% under the best conditions.…”

Catalytic Asymmetric Synthesis of Allylic Alcohols and Derivatives and their Applications in Organic Synthesis

“…[111] 108, which was obtained in good yield and enantiomeric excess, is a useful intermediate for the synthesis of bioactive compounds because of the diverse reactivity of the furan moiety. [112] 3.1.…”