ABSTRACT
A novel class of experimental fungicides has been discovered, which consists of special N-thiazol-4-yl-salicylamides. They originated from amide reversion of lead structures from the patent literature and are highly active against important phytopathogens, such as Phytophthora infestans (potato and tomato late blight), Plasmopara viticola (grapevine downy mildew) and Pythium ultimum (damping-off disease). Structure-activity relationship studies revealed the importance of a phenolic or enolic hydroxy function in the ß-position of a carboxamide. An efficient synthesis route has been worked out, which for the first time employs the carbonyldiimidazole-mediated Lossen rearrangement in the field of thiazole carboxylic acids.
Subject(s)
Fungicides, Industrial/chemical synthesis , Fungicides, Industrial/pharmacology , Oomycetes/drug effects , Salicylamides/chemical synthesis , Salicylamides/pharmacology , Thiazoles/chemical synthesis , Thiazoles/pharmacology , Dose-Response Relationship, Drug , Fungicides, Industrial/chemistry , Microbial Sensitivity Tests , Molecular Structure , Salicylamides/chemistry , Structure-Activity Relationship , Thiazoles/chemistryABSTRACT
A strategy aiming at the introduction of stereocenters into polymer-bound natural-product-derived and -inspired compound collections is presented. Treatment of immobilized aldehydes with Brown's pinene-derived allylboranes results in the stereoselective formation of homoallylic alcohols with up to 89 % ee (ee=enantiomeric excess). Subsequent iterative ozonolysis-allylation sequences with up to three allylations on a solid support give access to 1,3-polyols with different relative configurations. Esterification with acryloyl chloride and final ring-closing metathesis yields alpha,beta-unsaturated delta-lactones with multiply oxygenated side chains, a substructure found in a group of natural products with a broad range of biological activity. The flexibility of the approach is exemplified by the parallel synthesis of all eight diastereomers of cryptocarya diacetate on a solid support. The individual isomers are obtained in overall yields of 40-60 % over 10 steps and with 63-85 % diastereoselectivity for the major isomer.
Subject(s)
Allyl Compounds/chemistry , Biological Products/chemical synthesis , Combinatorial Chemistry Techniques , Lactones/chemical synthesis , Polymers/chemical synthesis , Cyclization , Models, Chemical , Molecular Mimicry , StereoisomerismABSTRACT
Enantiocomplementary allylation of solid phase-bound aldehydes gives rise to a natural product-derived compound collection, including all stereoisomers of cryptocarya diacetate.
Subject(s)
Acetates/chemistry , Biological Products/chemical synthesis , Combinatorial Chemistry Techniques , Cryptocarya/chemistry , Models, Chemical , Molecular Mimicry , StereoisomerismABSTRACT
A total synthesis of the structure corresponding to the novel tricyclic diterpene guanacastepene C has been realized in which a Knoevenagel cyclization serves as a key step to annulate the six-membered C-ring on a stereochemically secured bicyclic hydroazulene precursor.
Subject(s)
Bridged Bicyclo Compounds/chemistry , Cyclization , Diterpenes/chemical synthesis , Fungi/chemistry , Indicators and ReagentsABSTRACT
[reaction: see text] As a part of studies aimed toward the total synthesis of biologically important natural product guanacastepene A of contemporary interest, a new and concise route to a fully functionally endowed hydroazulenic core is delineated. The strategy involves the building of the requisite stereochemical features on a endo-tricyclo[5.2.1.0(2,6)]decane matrix and excision of the five-membered ring through a retro-Diels-Alder reaction. Generation of the seven-membered ring to access the hydroazulenic framework was achieved employing ring closure metathesis (RCM) reaction as the key step.
