A step-economical divergent approach to isoflavenes based on Suzuki-Miyaura cross coupling of a 3-boryl-2H-chromene with aryl bromides: application to total synthesis of isoflavonoid natural products.

We present a step-economical divergent synthetic approach for isoflavene derivatives using the Suzuki-Miyaura cross coupling of a 3-boryl-2H-chromene and three aryl bromides. 3-Boryl-2H-chromene, which is not a well-explored species, was prepared via Miyaura-Ishiyama borylation of a 3-chloro-2H-chromene obtained through a Claisen rearrangement cyclization cascade reaction. Further conversion of the cross-coupling products, three isoflavene derivatives, afforded three isoflavonoid natural products with one or two additional reaction steps.

4-Dimethylaminopyridine (DMAP), A Superior Mediator for Morita-Balylis-Hillman Reaction-Triggered Annulative Condensation of Salicylaldehydes and Acrylonitrile to Form 3-Cyano-2H-chromenes.

We unveiled superior base mediators for the annulative condensation of salicylaldehydes and acrylonitrile to give 3-cyano-2H-chromenes, which has been mediated only by 1,4-diazabicyclo[2.2.2]octane (DABCO) over the past two decades. The reactions were most efficiently mediated by 4-dimethylaminopyridine (DMAP), which yielded 3-cyano-2H-chromenes in higher yields than DABCO in most cases. We also confirmed that the reaction remained high yielding in a decagram-scale experiment with a catalytic amount of DMAP. The utility of this reaction was also exemplified by derivatization of an obtained 3-cyano-2H-chromene into a known 2H-chromene-3-carboxylic acid, which was previously synthesized with a non-readily available reagent.

Ligand-Dependant Selective Synthesis of Mono- and Dialkenylcarbazoles through Rhodium(III)-Catalyzed C-H Alkenylation.

The C-H alkenylation of N-acetylcarbazoles proceeds smoothly at the C1-position in the presence of a cationic Cp*Rh(III) catalyst to produce 1-alkenylcarbazoles. The use of a cationic CpE Rh(III) catalyst enables further alkenylation to give 1,8-dialkenylcarbazoles. The direct alkenylation procedure in combination with the ready removal of the acetyl directing group provides a straightforward synthetic pathway to 1- and/or 8-alkenyl-N-H-carbazole derivatives. One of 1-alkenyl-N-H-carbazoles obtained by the present C-H alkenylation/deacetylation exhibits solvatochromism.

Formylation Reaction of Amines Using N-Formylcarbazole.

Formamides are useful starting materials for pharmaceutical syntheses. Although various synthetic methods have been documented in this regard, the use of N-formylcarbazole as a formylation reagent for amines has not yet been reported. We report here the first examples of the use of N-formylcarbazole for the formylation of amines. The characteristic reactivity of N-formylcarbazole enables the selective formylation of sterically less hindered aliphatic primary and secondary amines. In contrast, sterically bulkier amines and weakly nucleophilic amines such as anilines are less reactive under the reaction conditions.

Production of Hydroxy Fatty Acids, Precursors of γ-Hexalactone, Contributes to the Characteristic Sweet Aroma of Beef.

Aroma is an essential factor for meat quality. The meat of Japanese Black cattle exhibits fine marbling and a rich and sweet aroma with a characteristic lactone composition. The mechanism of lactone formation associated with beef aroma has not been elucidated. In this study, we examined the precursors of γ-hexalactone, an indicator of the sweet aroma of beef and identified the mechanism underlying γ-hexalactone production. A low-temperature vacuum system was used to prepare beef tallow from Japanese Black cattle and Holstein cattle. The odor components were identified using headspace-gas chromatography. The analysis revealed that γ-hexalactone, γ-dodecalactone, δ-tetradecalactone, and δ-hexadecalactone were present as sweet aroma components of beef tallow prepared from marbling and muscle. Since we previously reported that γ-hexalactone formation correlates with linoleic acid content in beef, we analyzed ten oxidized fatty acids derived from linoleic acid by liquid chromatography-triple quadrupole mass spectrometry and detected two hydroxy-octadecadienoic acids (9S-HODE and 13S-HODE) in beef tallow. Significant differences in arachidonic acid 15-lipoxygenase and cyclooxygenase protein expression levels among subcutaneous fat, intramuscular fat, and muscle tissue were observed. Our results suggest that the combination of linoleic acid and the expression of lipid oxidase derived from beef muscle and intramuscular fat produce hydroxy fatty acids that result in a sweet aroma.

Expression of recombinant apopholasin using a baculovirus-silkworm multigene expression system and activation via dehydrocoelenterazine.

Pholasin is a photoprotein derived from the glowing bivalve mollusk, Pholas dactylus. Even though the chemical structure of the prosthetic group (chromophore) responsible for the light emission character of the mollusk remains unknown, research has shown that the presence of dehydrocoelenterazine (DCL) increased light emission and that the dithiothreitol adduct of DCL was isolated from Pholasin®. To date, our research has been focused on activating apopholasin, the naturally occurring apoprotein of Pholasin®, using DCL. In the current study, the expression of recombinant apopholasin via a baculovirus-silkworm multigene expression system is reported. Additionally, the purification of apopholasin using a Flag®-affinity column, the activation of apopholasin using DCL, and the initiation of its luminescent character through the addition of a peroxidase-hydrogen peroxide mixture are reported. The peroxidase-H2O2-dependent luminescence was observed from the recombinant apopholasin activated with DCL.

Catalytic Alkyne Arylation Using Traceless Directing Groups.

By using Pd0 /Mandyphos, we achieved a three-component aminoarylation of alkynes to generate enamines, which are then hydrolyzed to either α-arylphenones or α,α-diarylketones. This Pd-catalyzed method overcomes established known pathways to enable the use of amines as traceless directing groups for C-C bond formation.

Site-selective benzoin-type cyclization of unsymmetrical dialdoses catalyzed by N-heterocyclic carbenes for divergent cyclitol synthesis.

A highly site-selective N-heterocyclic carbene (NHC)-catalyzed benzoin-type cyclization of unsymmetrical dialdoses is developed to enable a divergent cyclitol synthesis. The choice of chiral NHCs and protecting groups affects the site-selectivity. The resulting inososes are converted into epi-, muco- and myo-inositols, and their chiral protected derivatives are formed in good yields.

Enhanced rate and selectivity by carboxylate salt as a basic cocatalyst in chiral N-heterocyclic carbene-catalyzed asymmetric acylation of secondary alcohols.

The rate and enantioselectivity of chiral NHC-catalyzed asymmetric acylation of alcohols with an adjacent H-bond donor functionality are remarkably enhanced in the presence of a carboxylate cocatalyst. The degree of the enhancement is correlated with the basicity of the carboxylate. With a cocatalyst and a newly developed electron-deficient chiral NHC, kinetic resolution and desymmetrization of cyclic diols and amino alcohols were achieved with extremely high selectivity (up to s = 218 and 99% ee, respectively) at a low catalyst loading (0.5 mol %). This asymmetric acylation is characterized by a unique preference for alcohols over amines, which are not converted into amides under the reaction conditions.