Anthony R. Gangloff

Synthesis of 3,5-disubstituted-1,2,4-oxadiazoles using tetrabutylammonium fluoride as a mild and efficient catalyst

Tetrabutylammonium fluoride (TBAF) was found to be a mild and efficient catalyst for the synthesis of 3,5-disubstituted-1,2,4-oxadiazoles. Using 0.1–1.0 equivalents of TBAF in THF for 1–24 h at room temperature, alkanoyl- and aroyloxyamidines were converted in high yield to the corresponding 3,5-disubstituted-1,2,4-oxadiazoles. A variety of R and R′ substituents were investigated.

Rhodium-catalyzed heterocycloaddition route to 1,3-oxazoles as building blocks in natural products synthesis

Abstract Rhodium(II) acetate serves as a catalyst for the heterocycloaddition reaction of diazodicarbonyl compounds with nitriles to give functionalized 1,3-oxazole derivatives in a simple one-step procedure. In particular, dimethyl diazomalonate undergoes this reaction to give 2-aryl-, 2-alkenyl-, or 2-alkyl-4-carbomethoxy-5-methoxy-1,3-oxazoles, and ethyl formyldiazoacetate (diazomalonate half-ester half-aldehyde) gives 2-aryl-, 2-alkenyl-, or 2-alkyl-4-carboethoxy-1,3-oxazoles. These products are of potential importance as key intermediates in the synthesis of several oxazole-containing natural products and other heterocyclic systems.

Synthesis of the oxazole- and diene-containing C9–C23 fragment of the type a streptogramin antibiotics

Abstract The right-hand portion (3) of the type A streptogramin antibiotics was synthesized in non-racemic form through use of a Horner-Wadsworth-Emmons reaction for diene construction, an asymmetric aldol condensation, and a zinc-promoted oxazole addition reaction.

Synthesis of macrocyclic lactam/lactone derivatives having antimicrobial activity

A number of new synthetic methods have been developed that are applicable to several types of antibiotics possessing macrocyclic lactone or lactam structures. These methods have permitted the synthe- sis of several key subunits of these compounds, and progress has been made on the total synthesis of some of these antibiotics. The type A streptogramin antibiotics have served as a special focus of these efforts. In addition, a combination of microbiological and chemical methods have been investigated for the direct modification of the naturally occurring antibiotics. Included among macrocyclic compounds of current biomedical interest are the streptogramin antibi- otics (l), the trienomycins (2), and the iejimalides (3). These compounds occur naturally as highly func- tionalized macrocyclic lactam or lactone systems. Madumycin I c1> is a representative member of the type A streptogramin series which comprises several antibiotics having wide-ranging applications. The trieno- mycins (2) and the iejimalides a show potent cytotoxicity in a variety of assays. The rich structural diversity of these compounds and their important biological activity has prompted us to use them as platforms for the development of new synthetic methods that may ultimately be applied to the total synthesis of these compounds and various analogues for further biomedical investigations. Con- siderable progress has been made in these efforts. In this brief paper, our results will be exemplified by our most recent progress on the synthesis of the streptogramin antibiotics. A more comprehensive description of our earlier work in this area has been published previously (4). Our basic strategy for the synthesis of the streptogramin antibiotics is shown for madumycin (Fig. 1). A number of new methods have been developed for the synthesis of the individual subunits shown in this strategy. Considerable attention was initially devoted to the types of functionalized 1,3-dienes and polyenes seen in 1 - 2, and a number of methods were investigated, especially through use of various pal- ladium-catalyzed reactions and new phosphonate reagents (5). Stereoselective routes were developed for the unsaturated acid subunit seen on the left of Fig. 1 through use of asymmetric aldol condensations and other approaches (6). A rhodium-catalyzed reaction of diazocarbonyl compounds with nitriles was devel- oped for the synthesis of 4-carboxy-1,3-oxazole derivatives as seen in all of the type A streptogramin antibiotics (7). Titanium- and zirconium-catalyzed lactamization reactions were also investigated which

Monocharged inhibitors of mast cell tryptase derived from potent and selective dibasic inhibitors

Truncation of potent and selective dibasic inhibitors afforded monocharged inhibitors of human mast-cell tryptase. Using two classes of analogues as lead structures, several monocharged derivatives were identified with K(i) values ranging from 0.084 to 0.21 microM against the enzyme.