Organic & Biomolecular Chemistry最新文献

Simple and sustainable three- and four-step sequences of di-OH-protection/mono-OMe-deprotection/OrgRC and di-OH-protection/mono-OMe-deprotection/OrgRC/OMe-deprotection protocols were developed to construct biologically active natural products of irisoquin, irisoquin A, irisoquin D, irisoquin F, sorgoleone-364, embelin, rapanone, 5-O-methylembelin, 5-O-methylrapanone and their analogues from the commercially available 2,5-dihydroxy-1,4-benzoquinone, aliphatic aldehydes and Hantzsch ester (1,4-DHP) in very good to excellent yields by using organocatalytic reductive coupling (OrgRC) as key reaction. Many of these natural compounds exhibited a broad spectrum of biological activities including antioxidant, anti-inflammatory, anticonvulsant, anxiolytic, analgesic, anthelmintic, antitumor, antibacterial, and antifertility properties. At the same time, simple and readily available 2,5-dihydroxy-1,4-benzoquinone was transformed into a functionally rich library of 2,5-dihydroxy-3,6-dialkyl-1,4-benzoquinones in very good yields by using sequential OrgRC followed by deprotection reactions and resulting natural/unnatural products would be excellent targets for investigation to show their biological activities compared to known natural products. Further, we tried to synthesize another mero-sesquiterpenoid of (+)-cyclospongiaquinone-1 from a chiral bicyclic aldehyde and hydroxy-1,4-benzoquinone by using OrgRC followed by etherification reactions, but we ended up with the synthesis of their ring-open analogues in good yields. The high-yielding gram-scale chemoselective synthesis of natural products irisoquin and demethylated-irisoquin demonstrated the potential to conduct these processes on larger scales.

Electrochemical oxidative cross-dehydrogenative-coupling (CDC) is an ideal strategy to conduct the C3-alkoxylation of imidazo[1,2-a]pyridine, but it remains a challenge owing to limitation imposed by the use of alkyl alcohols and carboxylic acids. Herein, we report a mild and efficient 2-electrode constant-potential electrolysis of imidazo[1,2-a]pyridine with hexafluoroisopropanol (HFIP) to produce various imidazo[1,2-a]pyridine HFIP ethers. Mechanistic studies indicated that the electrooxidation reaction might involve radical coupling and ionic reaction.

A novel H₂SO₄-catalyzed ANRORC-type rearrangement of pyrazinones to imidazoles proceeding through pyridazino[d]annulation with simultaneous introduction of a pyrazole ring at position 2 of the imidazole system has been developed, which offers efficient and expedited access to new biheterocyclic systems - 2-(pyrazol-3-ul)imidazoles and 2-(pyrazol-3-yl)imidazo[4,5-d]pyridazines. Diverse bi-N-heterocyclic systems with the imidazo[4,5-d]pyridazine-4,7-diamine moiety could be obtained in excellent yield when 5,6-dicyano-3-(2-oxo-2-ethyl)pyrazin-2(1H)-ones interact with hydrazines via the selective spiro-formation in a tandem ring-opening/ring-closing process, which allowed the simultaneous construction of five new C-N bonds. This new method is compatible with an array of functional groups, proceeds under mild reaction conditions with the involvement of commercially available reagents. Control experiments and DFT studies elucidate the detailed reaction mechanism.

An unsuccessful attempt to directly construct alkaloid iheyamine A from a fascaplysin framework resulted in the discovery of a novel synthetic approach to alkylated δ,γ-biscarboline derivatives. With the easy-to-operate reaction conditions of this protocol, 18 alkylated biscarbolines have been prepared in moderate to good yields. An unexpected domino transformation was proposed to involve a pyridinium ring-opening/aza-electrocyclization/oxidative deformylation sequence.

The present study describes the use of the di-tert-butyl dicarbonate (Boc₂O)/4-(N,N-dimethylamino)pyridine (DMAP) system for the amidation of carboxylic acids under neat conditions without heating. A set of carboxylic acids was explored, such as non-steroidal anti-inflammatory drugs (NSAIDs), fatty acids and protected prolines in the presence of aromatic, benzylic and aliphatic amines as nucleophilic partners. The scope of this easy approach was extended to the preparation of thirty-two diverse carboxylic amides, which were recovered with isolated yields varying from moderate to excellent. To increase the value of this protocol, a scalable chemoselective amidation of oleic acid with ethanolamine was successfully established. The corresponding fatty carboxylic amide, N-oleoylethanolamide (OEA), was recovered with 73% yield. This study highlights the potency of the use of mixed anhydrides formed in situ and the pursuit of the reaction profile reveals sequential steps rather than a one-pot process.

An atmospheric oxygen-mediated oxidative coupling of primary and secondary alcohols for the synthesis of nitrogen-containing heterocycles has been developed. This method utilizes atmospheric oxygen as the sole, environmentally friendly oxidant to convert a variety of alkyl and aromatic primary alcohols into aldehyde equivalents, avoiding over-oxidation to carboxylic acids. Notably, these mild oxidation conditions are compatible with both primary and secondary alkyl alcohols as substrates.

The nickel-catalyzed reaction of benzocyclic quaternary ammonium salts with arylzinc reagents or arylboron reagents affords amino-retentive arylation products in 40%-95% yields. This protocol is suitable for various substituted benzocyclic quaternary ammonium salts and arylzinc or arylboron reagents. The transition-metal-free reaction of benzocyclic quaternary ammonium salts with PhMe₂SiBpin in the presence of LiO^tBu leads to amino-retentive silylation products. 2-, 3-, 4-, 6-, and 7-position substituted 1,1-dimethyl-1,2,3,4-tetrahydroquinolin-1-ium triflates and 1,1-dimethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-ium triflate can be silylated in 34%-95% yields.

Benzothiazole and benzoxazole heterocyclic ring-containing 1,4,5-trisubstituted-1,2,3-triazoles are well known for their wide range of applications in pharmaceutical and medicinal chemistry, but their high-yielding metal-free selective synthesis has always remained challenging as no comprehensive simple protocol has been outlined to date. Owing to their structural and medicinal importance, herein, we synthesized various benzothiazole and benzoxazole heterocyclic ring-containing 1,4,5-trisubstituted-1,2,3-triazoles in high to excellent yields with chemo-/regioselectivity from the library of benzothiazole/benzoxazole-ketones and aryl/alkyl-azides through an enolate-mediated organocatalytic azide-ketone [3 + 2]-cycloaddition under ambient conditions in a few hours. The commercial availability or quick synthesis of the starting materials and catalysts, a diverse substrate scope, chemo-/regioselectivity, quick synthesis of pharmaceutically active known compounds and their analogues, and numerous medicinal applications of functionalized benzothiazole/benzoxazole-triazoles are the key attractions of this metal-free organo-click reaction.

Organoselenium compounds have been recognized as potential therapeutic agents against several diseases. Specifically, the incorporation of selenium into natural products has been reported to produce positive synergistic biological effects. We report herein the one-pot reaction of the natural monoterpenoid (-)-carvone with selenium bromide, which yields mentoselenophenone 1, together with minor amounts of phenols 2 and 3. A number of derivatives of 1 have also been prepared: the α,α dimer 6, oxime 7 and its Beckmann rearrangement product lactam 8. All except lactam 8 showed antioxidant GPx-like activity, with dimer 6 being the most active compound, followed by phenol 2 and oxime 7.

In this paper, we have uncovered a new reaction of N-homopropargylic β-enaminones, i.e. N-(4-phenyl-3-butynyl)-β-enaminones. When subjected to a reaction with excess molecular iodine or N-iodosuccinimide in the presence of cesium carbonate, N-homopropargylic β-enaminones afford 6,7-dihydrofuro[3,4-c]pyridines in low to moderate yields. The generation of two new C/O-C bonds during the reaction leads to the construction of unknown heterobicyclic 5,6-fused ring systems. In some reactions, 3,4-diaryloylpyridines are also observed in low yields. During the formation of 3,4-diaryloylpyridines, a new carbonyl (ketone) group is generated. The synthesized 6,7-dihydrofuro[3,4-c]pyridines and 3,4-diaryloylpyridines may be of use in pharmaceutical and medicinal chemistry as new and novel molecular entities and structural leads.