Stereochemical Determination of the Leupyrrins and Total Synthesis of Leupyrrin A₁

Abstract

The stereochemical determination of the potent antifungal agents leupyrrin A1 and B1 and the total synthesis of leupyrrin A1 are reported. The relative and absolute configuration was determined by a combination of high field NMR studies, molecular modeling, and chemical derivatization. The expedient total synthesis involves a one-pot sequential Zr-mediated oxidative diyne-cyclization/regioselective opening sequence for preparation of the unique dihydrofuran ring, a highly stereoselective one-pot approach to the butyrolactone, a challenging sp(2)-sp(3) Suzuki coupling and a high-yielding Shiina macrolactonization.

Iodoarene-catalyzed cyclizations of N-propargylamides and β-amidoketones: synthesis of 2-oxazolines

“…This would provide two complementary routes to substituted 2-oxazolines, which are valuable heterocycles found in ligand scaffolds, natural products such as the leupyrrins [18–19], and potential pharmaceuticals (Fig. 1) [20–22].…”

Versatile Photochemical Reactivity of Diverse Substituted 2‐, 4‐ and 5‐(o‐Vinylstyryl)oxazoles

“…[1,2] derivatives. We synthesized new 4-methyl-2-(2-vinylstyryl)oxazole (1), 4-methyl-5-(2-vinylstyryl)oxazole (2), 2-methyl-4-(2-vinylstyryl)oxazole (3), and 2-phenyl-5-(2-vinylstyryl)oxazole (4). [8] There are various methodologies and synthetic approaches for the synthesis of the oxazole ring incorporated into diverse skeletons [9] because the oxazole structure is commonly found in a vast number of natural products and pharmaceuticals.…”

“…The study of the 5-tolyl-, 4,5-diphenyland 4-phenyl-5-methyl-2-(2-vinylstyryl)oxazole showed that the phenyl substituent on the 4-position in the oxazole ring has a high impact on the overall electron density distribution in the molecule and on the photocyclization process (Scheme 1). [2] New routes to oxazoline derivatives are more than welcome because of the presence of the oxazoline ring in ligand scaffolds, natural products [3,4] and potential pharmaceuticals. The oxo-bridged photoproducts E could further be easily converted into benzo[f ]qouinolines (Scheme 1).…”

Total Synthesis of Leupyrrins A1 and B1, Highly Potent Antifungal Agents from the Myxobacterium Sorangium cellulosum

“…These structures also contain ap yrrole, an oxazoline, and ad iacid fragment as additional characteristic features together with aside chain that is attached to the oxazoline moiety. [8] Leupyrrin A 1 has demonstrated highly potent antifungal properties against Rhodotorula glutinis, Aspergillus niger, Botrytis cinerea,a nd Mucorh iemalis with minimum inhibitory concentration( MIC) values in the submicromolar range and antiproliferative activities against mousef ibroblast cells. They contain up to seven stereogenic centers,w hich have been recently assigned in our group by extensive NMR studies in combination with molecular modeling and chemical methods.…”

“…[8,10,11] Here, we describe, in full detail,t he design, evaluation and elaborationo ft he variouss ynthetic tactics that we pursued to access the unique three-dimensional architecture of the leupyrrins. [8,10,11] Here, we describe, in full detail,t he design, evaluation and elaborationo ft he variouss ynthetic tactics that we pursued to access the unique three-dimensional architecture of the leupyrrins.…”