Baker-Venkataraman Rearrangement Research Articles

Applications of Baker-venkataraman Rearrangement in the Synthesis of Promising Organic Molecules

Abstract:: In organic synthesis, carbon-carbon bond formation is the fundamental transformation to create the carbon backbone of organic molecules and this key reaction is very popular in the improvement of organic chemistry, which exists at the bottom of the heart of the chemical sciences. The Baker- Venkataraman rearrangement has received great attention in the formation of 1,3-diketones through the regioselective construction of carboncarbon bonds. This rearrangement is an important type of chemical transformation in which the intramolecular migration of the ester acyl group takes place to provide 1,3-diketones in the presence of the base. Generally, 1,3-diketones or ortho-hydroxydibenzoylmethane derivatives undergo cyclization to provide the corresponding flavones in the presence of concentrated sulfuric acid. The Baker-Venkataraman rearrangement is frequently employed in the preparation of flavones and chromones. Besides, anthrapyran and anthracyclin antibiotics, benzopyrans, coumarins, xanthones, etc., are also synthesized with the help of these reactions. This review deals with the brilliant application of the Baker-Venkataraman rearrangement in the synthesis of promising organic compounds.

Choline hydroxide, an efficient, green, and recyclable base catalyst, promoted the synthesis of 3-aroylflavones via Baker–Venkataraman rearrangement

ABSTRACT 3-Aroylflavones, a new synthesized group of flavones, have been recently studied via Baker–Venkataraman rearrangement under ‘one-pot’ or sequential ‘one-pot’ reaction conditions. Choline hydroxide, an inexpensive, easily prepared, and green homogeneous catalyst has been found to be the most efficient catalyst among several base catalysts such as KOH/pyridine, KOH/triethylamine, and CaO-ES/triethylamine in the sequential ‘one-pot’ synthesis of 3-aroylflavones. Moreover, the catalyst’s efficiency, and high recyclability to six times without considerable loss of 3-aroylflavones have enhanced the importance of the procedure. Furthermore, 1D-NMR, 2D-NMR, and HRMS have also been used to elucidate the structures of synthesized compounds.

Total syntheses and antibacterial evaluations of cudraflavones A-C and related Flavones

The total syntheses of the natural prenylated flavones cudraflavones A–C (1–3), artoheterophyllin D (28) and artelasticin (29) are reported, along with the evaluations of their antibacterial activities. The key steps of the synthesis involved a Baker-Venkataraman rearrangement and an intramolecular cyclization for the construction of the flavone core and the regioselective formation of the pyran and isopentenyl scaffolds. The tested natural flavones 1–3 and 27–29 exhibited potent activity against S. aureus ATCC 29213, S. epidermidis ATCC 14990, E. faecalis ATCC 29212 and B. subtilis ATCC 6633 with MIC values ranging from 0.125 μg/mL to 16 μg/mL. Compound 3 displayed the strongest potency, with MIC values in the range between 0.125 and 1 μg/mL, as a potential candidate to combat G+ bacterial infections. Preliminary mechanism of action studies suggested that this compound killed bacteria by disrupting bacterial membrane integrity.

Visible-Light Mediated Radical Alkylation of Flavones: A Modular Access to Nonsymmetrical 3,3″-Biflavones.

The first synthetic strategy for nonsymmetrical 3,3″-biflavones is described. To this end, a novel visible-light iridium-catalyzed radical C-3 alkylation of flavones with o-methoxy phenacyl bromides was developed. Selective demethylation of the alkylated flavones and acylation through a Baker-Venkataraman rearrangement with diverse acyl chlorides afforded a library of 20 structurally novel biflavones. This modular strategy rapidly expands the structural complexity and diversity of these privileged scaffolds.

Total Syntheses and Antibacterial Evaluations of Neocyclomorusin and Related Flavones.

Neocyclomorusin (1), a natural bioactive pyranoflavone mainly isolated from plants of the Moraceae family, was synthesized for the first time using a Friedel-Crafts reaction, a Baker-Venkataraman (BK-VK) rearrangement, a selective epoxidation, and a novel SN2-type cyclization as the key steps. The present protocol was also successfully applied for the total synthesis of oxyisocyclointegrin (2). Structurally related natural products morusin (23) and cudraflavone B (24) were also prepared. We investigated the antibacterial activities of these natural compounds against both Gram-negative and Gram-positive strains. The prenylated flavones, morusin (23) and cudraflavone B (24), showed comparable activity to ampicillin and kanacycin A against Staphylococcus aureus. Both morusin (23) and cudraflavone B (24) showed better antibacterial activities than ampicillin against the Gram-positive bacteria Staphylococcus epidermidis and Bacillus subtilis. Both neocyclomorusin (1) and oxyisocyclointegrin (2) displayed disappointing antimicrobial activities against Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, and Bacillus subtilis strains.

Synthesis, Characterization and Biological Activities of Pyrazole Based Heterocycles

In this work, a unique pyrazolyl compounds comprising flourine and thiophene were synthesized. In brief, esters 3a-f were synthesized by reacting thiophene and pyrazolyl acid (1) with various 2-hydroxyacetophenones (2a-f). The 1,3-diketones 4a-f were formed by Baker- Venkataraman rearrangement of esters 3a-f. Compounds 4a-f were cyclized to form chromene derivatives 5a-f, which further converted into pyrazolyl derivatives 6a-f. The majority of the compounds in series 3a-f, 4a-f, 5a-f and 6a-f showed promising antibacterial activity against S. typhii, S. aureus, B. subtilis and E. coli. Compounds 4e and 4f exhibited considerable antifungal activity against A. niger, while the majority of the compounds had promising activity against T. viride. At 1 mg/mL concentration, some of the synthesized compounds shown potential α-amylase inhibitory action.

Synthesis and Biological Evaluation of 2-(4,5,6,7-Tetrahydrobenzo[c]Isoxazol-3-yl)-4H-Chromen-4-Ones

A new series of 2-(4,5,6,7-tetrahydrobenzo[c]isoxazol-3-yl)-4H-chromen-4-ones 5a-e were synthesized from 1-(2-hydroxyphenyl)-3-(4,5,6,7-tetrahydrobenzo[c]isoxazol-3-yl)propane-1,3-diones 4a-e in presence of acetic acid and conc. HCl. Compounds 4a-e were synthesized by Baker-Venkataraman rearrangement from 2-acetylphenyl 4,5,6,7-tetrahydrobenzo[c]isoxazole-3-carboxylate 3a-e in presence of pyridine and KOH and compounds 3a-e were synthesized from 4,5,6,7-tetrahydrobenzo[c]isoxazole-3-carboxylic acid 1 and substituted 2-hydroxy acetophenone 2a-e. All the synthesized compounds were characterized with the help of IR, 1H NMR, 13C NMR and mass spectroscopic techniques. All the compounds were screened for their in vitro anti-inflammatory activities. Furthermore, molecular docking study against COX-2 enzyme could provide valuable insight into the binding affinity of these molecules and the type of thermodynamic interactions governing their binding.

The synthesis and biological evaluation of A- and B-ring fluorinated flavones and their key intermediates

An efficient three-step method for the synthesis of new polyfluoroflavones has been proposed using substituted benzoyl chlorides and 2-hydroxyacetophenone to form the initial 2-(polyfluoroaroyloxy)acetophenones, which are transformed into 1,3-diaryl-1,3-diketones as a result of the Baker-Venkataraman rearrangement. The ability of these 1,3-diketones to undergo keto-enol and ring-chain tautomerism was found, depending on the nature of the solvent. Under acid- or base-catalyzed conditions the alternative cyclization routes of fluorine-containing 1,3-diaryl-1,3-diketones into A- and B-ring halogenated flavones have been reported. The anti-influenza and fungistatic effects of the synthesized compounds were evaluated, and products with promising antimicrobial properties were found.

Total Synthesis of Mulberry Diels-Alder-Type Adducts Kuwanons G and H.

Mulberry Diels-Alder-type adducts (MDAAs) are a group of rare natural polyphenols biosynthetically derived from [4 + 2]-cycloaddition of chalcones and dehydroprenylphenols. In this study, kuwanons G (1) and H (2), two bioactive MDAAs with unique dehydroprenylflavonoid dienes, were totally synthesized for the first time in a biomimetic manner. The key features of the convergent route include the use of the Baker-Venkataraman rearrangement, alkylation of β-diketone, intramolecular cyclization, and Suzuki-Miyaura coupling to achieve the subunit diene.

One-Pot Green Synthesis of 2-Hydroxybenzoyl(cinnamoyl)methanes and 2-Styrylchromones Using Dual-Frequency Ultrasonication

One-pot green synthesis of (2-hydroxybenzoyl)(cinnamoyl)methanes has been performed by reacting 2-hydroxyacetophenones with cinnamoyl chlorides using activated Ba(OH)2, followed by Baker–Venkataraman rearrangement assisted by dual-frequency ultrasonication. Cyclization of (2-hydroxybenzoyl)(cinnamoyl)methanes using methanesulfonic acid along with dual-frequency ultrasound irradiation resulted in the formation of 2-strylchromones in a single step. The products were obtained with high yields, and their structures were confirmed by NMR and IR spectral data.

Soft-enolization Baker-Venkataraman Rearrangement Enabled Total Synthesis of Dirchromones and Related 2-Substituted Chromones.

A seven-step total synthesis of the original scaffold of cytotoxic dirchromones involving an unprecedented soft-enolization Baker-Venkataraman rearrangement was designed. The methodology enabled access to naturally occurring dirchromone 1 (21% overall yield) at gram-scale, which was screened for cytotoxicity against 13 cancer cell lines. The scope of the soft-enolization Baker-Venkataraman rearrangement encompasses diversely substituted dirchromones, including flavonoids, 2-styrylchromones, and 2-phenylethylchromones.

SYNTHESIS AND ANTIPROLIFERATIVE ACTIVITY OF FLAVONOID DERIVATIVES: EFFECT OF B-RING SUBSTITUTION

Flavones, flavonols, flavanones and isoflavones constitute four important categories of naturally occurring flavonoids. These compounds possess good antiproliferative activity and can act as adjuvants to existing anticancer therapy. We have synthesized twenty synthetic flavonoids including flavones, flavonols, flavanones and isoflavones using Claisen-Schmidt condensation, Baker-Venkataraman rearrangement and related reactions. The synthesized compounds were evaluated for antiproliferative activity against MCF-7, K562 and HepG2 cell lines. Flavanones showed good activity against HepG2 cell lines whereas some flavones and isoflavones were active in inhibiting the growth of K562 and MCF-7 cell lines. The study underlines the importance of electron rich substituents on the B-ring of synthetic flavonoids.

Formal total synthesis of stigmatellin A

An efficient and stereoselective approach for the formal total synthesis of Stigmatellin A has been described. The key steps involved in this synthesis are desymmetrization of the bicyclic olefin to introduce two methyl and two hydroxyl chiral centers, Friedel Crafts acylation, regioselective demethylation, Baker-Venkataraman rearrangement and Grubbs cross metathesis.

Total Synthesis of the Naturally Occurring Glycosylflavone Aciculatin.

The new flavone-glycoside aciculatin (1), from Chrysopogon aciculatus, has been shown to have cytotoxic, anti-inflammatory, and antiarthritis activity. Further biological studies have been limited because of the limited availability of 1 from natural sources. Herein the first total synthesis of 1 in an overall yield of 8.3% is described. The synthesis involved the regio- and stereoselective glycosylation-Fries-type O-to-C rearrangement to construct the C-aryl glycosidic linkage, followed by a Baker-Venkataraman rearrangement and cyclodehydration to form the flavone scaffold.

ChemInform Abstract: One‐Pot Synthesis of Benzopyran‐4‐ones with Cancer Preventive and Therapeutic Potential.

AbstractThe title benzopyranones are prepared by a tandem sequence involving the organobase‐catalyzed Michael addition of R1COCH2COR2 to chromonecarboxylic acid leading to decarboxylation followed by a Baker—Venkataraman rearrangement of the resulting Michael—adducts via chromone‐ and/or chromanone ring closure when R1 is an ortho‐hydroxyaryl group.

ChemInform Abstract: Total Synthesis of the Antiviral Natural Product Houttuynoid B.

Abstracta constituent of the Chinese plant Houttuynia cordata

Novel chromone and xanthone derivatives: Synthesis and ROS/RNS scavenging activities

Chromones and xanthones are oxygen-containing heterocyclic compounds acknowledged by their antioxidant properties. In an effort to develop novel agents with improved activity, a series of compounds belonging to these chemical classes were prepared. Their syntheses involve the condensation of appropriate 2-methyl-4H-chromen-4-ones, obtained via Baker-Venkataraman rearrangement, with (E)-3-(3,4-dimethoxyphenyl)acrylaldehyde to provide the corresponding 2-[(1E,3E)-4-(3,4-dimethoxyphenyl)buta-1,3-dien-1-yl]-4H-chromen-4-ones. Subsequent electrocyclization and oxidation of these compounds led to the synthesis of 1-aryl-9H-xanthen-9-ones. After cleavage of the protecting groups, hydroxylated chromones and xanthones were assessed as scavenging agents against both reactive oxygen species (ROS) [superoxide radical (O2•-), hydrogen peroxide (H2O2), hypochlorous acid (HOCl), singlet oxygen (1O2), and peroxyl radical (ROO•)] and reactive nitrogen species (RNS) [nitric oxide (•NO) and peroxynitrite anion (ONOO−)]. Generally, all the tested new hydroxylated chromones and xanthones exhibited scavenger effects dependent on the concentration, with IC50 values found in the micromolar range. Some of them were shown to have improved scavenging activity when compared with previously reported analogues, allowing the inference of preliminary conclusions on the structure–activity relationship.

Total Synthesis of the Antiviral Natural Product Houttuynoid B

The first total synthesis of houttuynoid B, a powerful antiviral flavonoid glycoside from the Chinese plant Houttuynia cordata, is described. In a key step, a Baker-Venkataraman rearrangement employing an already glycosylated substrate was used to efficiently set up the fully functionalized carbon skeleton. The required benzofuran building block was prepared through a domino Sonogashira coupling/5-endo-dig cyclization and converted into a stable 1-hydroxybenzotriazole-derived active ester prior to linking with a galactosylated hydroxyacetophenone unit. The elaborated synthesis requires only nine steps (11 % overall yield) along the longest linear sequence and paves the way for the preparation of structurally related compounds for further biological evaluation.

A New Protocol for Total Synthesis of Natural Product Frutinone A and Its Derivatives

A new protocol for total synthesis of natural product frutinone A was accomplished in three steps by using inexpensive 2′-hydroxyacetophenone as starting material. The key intermediate 3-(2-chlorobenzoyl)-4-hydroxycoumarin was synthesized in one pot through Baker–Venkataraman rearrangement of 2-acetylphenyl 2-chlorobenzoate followed by introduction of methyl chloroformate under basic conditions. Then, base-promoted intramolecular nucleophilic substitution reaction of 3-(2-chlorobenzoyl)-4-hydroxycoumarin provided frutinone A in excellent yield. The synthetic route features good yield, transition metal-free and mild reaction conditions, and high tolerance for functionality, thereby allowing easy substitutions around the frutinone A core.

ChemInform Abstract: A Baker—Venkataraman Retro‐Claisen Cascade Delivers a Novel Alkyl Migration Process for the Synthesis of Amides.

AbstractIf water is not strictly excluded the initially formed Baker—Venkataraman rearrangement products of substrates (I) undergo retro‐Claisen rearrangement to form amides (II).