Silver Benzoate Facilitates the Copper-Catalyzed C-N Coupling of Iodoazoles with Aromatic Nitrogen Heterocycles.

In the literature, C-N coupling methods for the reaction of iodo-oxazole with 2-pyridinone were found to be low yielding. C-N coupling using silver benzoate additives with CuI catalysts and 4,7-dimethoxy-1,10-phenanthroline ligands has been developed to afford synthetically useful yields of the desired heterobicycle product. The reaction conditions are applied to the coupling of a range of iodo-heterocycles with 2-pyridinone. The coupling of a variety of NH-containing heterocycles with 4-iodo-oxazole is also demonstrated. The use of 2-, 4-, or 5-iodo-oxazole allows for the coupling of pyridinone to each oxazole position.

ß-Carboline Amides as Intrinsic Directing Groups for C(sp2)-H Functionalization.

Many site-selective palladium-catalyzed C-H functionalization methods require directing groups. We report here ß-carboline amides as intrinsic directing groups for C(sp2)-H functionalization. Various substrates including the natural product alangiobussinine and the marinacarboline core structure were functionalized using carboline-directed δ-C(sp2)-H alkynylations. This transformation proceeds under mild conditions and is compatible with a wide variety of ß-arylethamines. δ-Alkynylation of ß-arylethamines via a six-membered palladacycle is favored over γ-C(sp2)-H bond functionalization when both positions are accessible. The versatility of ß-carboline amides as directing groups is evidenced by other δ-C(sp2)-H functionalizations such as alkenylation, arylation, and C-N bond formation.

Stereodivergent Intramolecular C(sp(3))-H Functionalization of Azavinyl Carbenes: Synthesis of Saturated Heterocycles and Fused N-Heterotricycles.

A general approach for the formation of five-membered saturated heterocycles by intramolecular C(sp(3))-H functionalization is reported. Using N-sulfonyltriazoles as Rh(II) azavinyl carbene equivalents, a wide variety of stereodefined cis-2,3-disubstituted tetrahydrofurans were obtained with good to excellent diastereoselectivity from readily available acyclic precursors. The reaction is shown to be amenable to gram scale, and judicious choice of reaction conditions allowed for stereodivergence, providing selective access to the trans diastereomer in good yield. The resulting products were shown to be valuable intermediates for the direct preparation of fused N-heterotricycles in one step by intramolecular C-H amination or Pictet-Spengler cyclization.

Tomato Cutin Deficient 1 (CD1) and putative orthologs comprise an ancient family of cutin synthase-like (CUS) proteins that are conserved among land plants.

The aerial epidermis of all land plants is covered with a hydrophobic cuticle that provides essential protection from desiccation, and so its evolution is believed to have been prerequisite for terrestrial colonization. A major structural component of apparently all plant cuticles is cutin, a polyester of hydroxy fatty acids; however, despite its ubiquity, the details of cutin polymeric structure and the mechanisms of its formation and remodeling are not well understood. We recently reported that cutin polymerization in tomato (Solanum lycopersicum) fruit occurs via transesterification of hydroxyacylglycerol precursors, catalyzed by the GDSL-motif lipase/hydrolase family protein (GDSL) Cutin Deficient 1 (CD1). Here, we present additional biochemical characterization of CD1 and putative orthologs from Arabidopsis thaliana and the moss Physcomitrella patens, which represent a distinct clade of cutin synthases within the large GDSL superfamily. We demonstrate that members of this ancient and conserved family of cutin synthase-like (CUS) proteins act as polyester synthases with negligible hydrolytic activity. Moreover, solution-state NMR analysis indicates that CD1 catalyzes the formation of primarily linear cutin oligomeric products in vitro. These results reveal a conserved mechanism of cutin polyester synthesis in land plants, and suggest that elaborations of the linear polymer, such as branching or cross-linking, may require additional, as yet unknown, factors.

Synthesis of tocopheryl succinate phospholipid conjugates and monitoring of phospholipase A2 activity.

Tocopheryl succinates (TOSs) are, in contrast to tocopherols, highly cytotoxic against many cancer cells. In this study the enzyme activity of secretory phospholipase A(2) towards various succinate-phospholipid conjugates has been investigated. The synthesis of six novel phospholipids is described, including two TOS phospholipids conjugates. The studies revealed that the TOS conjugates are poor substrates for the enzyme whereas the phospholipids with alkyl and phenyl succinate moieties were hydrolyzed by the enzyme to a high extent.

The identification of cutin synthase: formation of the plant polyester cutin.

A hydrophobic cuticle consisting of waxes and the polyester cutin covers the aerial epidermis of all land plants, providing essential protection from desiccation and other stresses. We have determined the enzymatic basis of cutin polymerization through characterization of a tomato extracellular acyltransferase, CD1, and its substrate, 2-mono(10,16-dihydroxyhexadecanoyl)glycerol. CD1 has in vitro polyester synthesis activity and is required for cutin accumulation in vivo, indicating that it is a cutin synthase.