Prenyl Ethers Research Articles

Yb(OTf)3-Catalyzed and Di-tert-butyl Dicarbonate-Mediated Decarboxylative Etherification and Esterification Reactions.

Protecting group chemistry has invariably captured the fascination of chemists because of its extensive viability in chemical synthesis. The present report describes our pioneer work of applying ytterbium triflate as a catalyst, for the reaction of alcohols with di-tert-butyl dicarbonate (Boc2O) leading to the formation of tert-butyl ethers. There exists no recorded evidence for the use of Yb(OTf)3 as a catalyst for the protection of alcohols to tert-butyl ethers, despite its excellent utility in various reactions. Yb(OTf)3 has been used predominantly in the catalytic deprotection studies such as selective deprotection of tert-butyl esters to carboxylic acids as well as prenyl ethers to alcohols. This study involved the critical evaluation of solvent, time, and temperature that finally led to an efficient protocol for the formation of tert-butyl ethers. Yb(OTf)3 catalyzed the formation of tert-butyl ethers, notably reducing the reaction time, which is exemplified by the achievement of up to 92% conversion of alcohols to tert-butyl ethers within an hour. Additionally, the report demonstrates the utility of this synthetic protocol for the protection of carboxylic acids.

Flavonoids from Artocarpus hirsutus Lam: Synthesis of new prenyl ethers, acetates and their anti-acne activity

AbstractArtocarpus hirsutus Lam., one of the species of Artocarpus, is not well studied. The present study is intended to isolate the chemical constituents present in stem wood extract of A. hirsutus, to synthesize their new derivatives and to evaluate their activity against Propionibacterium acnes. Three major flavonoids, cudraflavone A, cycloartocarpin and artocarpin were isolated from the stem wood extract and cudraflavone A was isolated for the first time from this plant. New prenyl ether and acetate derivatives of isolated flavonoids have been synthesized. This is the first to report on the evaluation of in vitro anti-acne potential of crude extracts, isolated flavonoids and their new synthetic derivatives. The crude extracts (MIC values 2, 4 and 15.6 μg/mL) and the isolated constituents (MIC values 2, 0.5 and 0.25 μg/mL) showed significant in vitro anti-acne activity against P. acnes which was comparable with commercially available anti-acne agent, tea tree, oil and a standard antibiotic, Clindamyci...

Allyl and prenyl ethers of mansonone G, new potential semisynthetic antibacterial agents

Four natural 1,2-naphthoquinones: mansonones C, E, G, and H were isolated from the dichloromethane extract of Mansonia gagei Drumm. heartwoods. Mansonone G was further converted to eight ether and four ester analogues. The structures of mansonones and the analogues were well-confirmed by spectroscopic techniques. All compounds were evaluated for their antibacterial activity against Gram-positive and negative bacteria. Further modification of mansonone G furnished certain analogues displaying better activity than natural mansonones. Particularly, allyl and prenyl ethers of mansonone G exhibited better activity against Staphylococcus aureus with MIC sixty-four times better than their natural compound.

ChemInform Abstract: Microwave‐Promoted Deprenylation: Prenyl Ether as a Thermolabile Phenol Protecting Group.

ChemInform Abstract: Microwave‐Promoted Deprenylation: Prenyl Ether as a Thermolabile Phenol Protecting Group.

ChemInform Abstract: Synthesis of Allyl‐ and Prenylcoumarins via Microwave‐Promoted Tandem Claisen Rearrangement/Wittig Olefination.

AbstractA broad range of allyl, dimethylallyl, crotyl and prenyl ethers of variously substituted aromatic 2‐hydroxy carbonyl compounds are transformed according to the title reaction in the presence of a phosphorylide to form 6 or 8‐allylated or prenylated coumarine derivatives.

ChemInform Abstract: Tandem Claisen Rearrangement/6‐endo Cyclization Approach to Allylated and Prenylated Chromones.

AbstractAllyl, dimethylallyl, and prenyl ethers of ortho‐acylphenols react upon microwave irradiation to form C‐allylated or ‐prenylated chromones.

Microwave-Promoted Deprenylation: Prenyl Ether as a Thermo­labile Phenol Protecting Group

<i>para</i>-Substituted aryl prenyl ethers undergo a deprenylation reaction upon microwave irradiation. This offers the opportunity to use a prenyl ether as a thermolabile protecting group in the synthesis of natural products with a chromone structure, which proceeds via a tandem deprenylation/6-<i>endo</i>-cyclization sequence.

Tandem Claisen Rearrangement/6‐endo Cyclization Approach to Allylated and Pren­ylated Chromones

AbstractAllyl, dimethylallyl and prenyl ethers derived from o‐acylphenols reacted upon microwave irradiation to form C‐allylated or ‐prenylated chromone derivatives, depending on the substitution pattern of the arene and the allyl substituent. The reaction proceeds through a tandem Claisen rearrangement and 6‐endo‐trig or 6‐endo‐dig cyclization sequence. For prenyl ethers, the tandem sequence can be extended by a Cope rearrangement to furnish 6‐prenylchromones. The method is potentially useful for the synthesis of natural products and drugs.

Synthesis of Allyl- and Prenylcoumarins via Microwave-Promoted Tandem Claisen Rearrangement/Wittig Olefination

Allyl, dimethylallyl, crotyl, and prenyl ethers of various aromatic <i>ortho</i>-hydroxy carbonyl compounds undergo a tandem sequence of Claisen rearrangement, carbonyl olefination, and cyclization upon microwave irradiation in the presence of a stabilized ylide. The products are multiply substituted 6- or 8-allylated or prenylated coumarins (2<i>H</i>-chromen-2-ones).

An Efficient First Synthesis of Licochalcone G

Chalcones (1,3-diarylpropenones) constitute one of the major classes of flavonoids with widespread distribution in plant kingdom. Prehistoric therapeutic applications of these small and nonchiralmolecules can be associatedwith the 1000-yearold use of plants and herbs for the treatment of different medical disorders. Chalcones have a conjugated double bond and an entirely delocalized π-electron system on both benzene rings which attributes nonlinear optical properties to them. Several natural and nonnatural chalcones have been investigated as anti-inflammatory, anti-oxidant, antimicrobial, antiprotozoal (antileishmanial and antitrypanosomal), anticancer, antibacterial, antiviral, antihyperglycemic, antiplatelet, anti-ulcerative, antitubercular, antiangiogenic, and antiplasmodial agents. They have also shown inhibitory effects on several enzymes. Chalcones are important precursors in the biosynthesis of flavones and flavanones. The chemistry and therapeutic applications of chalcones have triggered extensive and enduring efforts toward the syntheses of these important compounds throughout the world. Licochalcone G (7, Figure 1) was isolated from the acetone extract of Glycyrrhiza inflata. G. inflata is the main species in licorice, contains numerous retrochalcones and showed various biological properties. Licorice has been used by human beings for over 4000 years and it appears as a component herb in about 60% of traditional Chinese medicine prescriptions. LicochalconeG (7) showed anti-influenza (H1N1 swine influenza) activity. To date, synthesis of this important chalcone was not reported in the literature. Previously, we have reported the synthesis of licochalcones A–E (1–5). In continuation of our work on the synthesis of these bioactive natural products and their derivatives, herein we wish to describe the first synthesis of licochalcone G (7) using water-accelerated [3,3]-sigmatropic rearrangement and Claisen–Schmidt condensation as key steps. Retrosynthetic approach for licochalcone G (7) synthesis is depicted in Scheme 1. We envisaged that the target molecules could be achieved from intermediate 8 by deprotection. Compound 8 could easily be prepared from compounds 9 and 10 by means of Claisen–Schmidt condensation. Compound 9 could be obtained from 2,4,-dihydroxyacetophenone (11) whereas compound 10 could be prepared from 4-hydroxy-2-methoxy benzaldehyde (12). Accordingly, we commenced the synthesis from 2,4,dihydroxyacetophenon (11). As shown in Scheme 2, allyl protection of compound 11 using K2CO3/NaI system in DMF at 60 C afforded the diallyl protected 2,4dihydroxyacetophenone 9 in 98% yield. Next, treatment of 4-hydroxy-2-methoxy benzaldehyde (12) with 1-bromo-3methyl-2-butene (prenyl bromide) in the presence of K2CO3 in acetone under reflux condition gave compound 13 in 97% yield. The aryl prenyl ether 13 was then subjected to water-accelerated [3,3]-sigmatropic rearrangement reaction using EtOH/H2O (v/v = 4/1) in pressure tube afforded the product 14 in 53% yield. The phenolic OH group of compound 14 was protected as ethoxymethyl aryl ether (EOM O Ar). The choice of protecting group is quite important in the chalcone synthesis in many aspects such as yield, migration, deprotection, etc. Treatment of compound 14 with chloromethyl ethyl ether (EOM Cl) using K2CO3 in DMF at room temperature resulted the compound 10 in 81% yield. Claisen–Schmidt condensation of compound 9 and10using ethanolicKOHat room temperature in 15 hproduced the protected chalcone 8 in 52% yield. The transconfiguration was confirmed with coupling constant (J = 16.2 Hz) between the two doublet signals at δ 7.98 and 7.56, a presentative coupling pattern for the protons in the conjugated alkene system. Treatment of compound 8withDowex resin in anhydrous methanol at room temperature gave the EOM-free chalcone in 60% yield. Finally, allyl group deprotection was achieved using K2CO3 and catalytic amount of Pd(PPh3)4 (2 mol %) in anhydrous MeOH at 60 C to furnish the desired natural chalcone licochalcone G in 85% yield. In conclusion, we have developed an efficient approach for the first synthesis of licochalcone G. Water-accelerated [3,3]sigmatropic rearrangement and Claisen–Schmidt condensation are the key transformations of the present method. We feel, the present synthetic route may find application for the construction of different natural and nonnatural chalcones of this kind.

Prenyl Ethers: Novel Fungal Volatiles Formed by Penicillium digitatum.

Prenyl ethyl ether (PEE) was previously described as the cause for a solvent-like off-note in ground hazelnuts, but its origin remained unclear. Investigations were carried out by analytical groups of Coop and Givaudan over four years to elucidate this phenomenon. From mouldy citrus fruits a strain of Penicillium digitatum was isolated and found to form PEE. Formation on citrus and other fruits was prominent and contributed to the particular smell of decayed fruits. Several strains of P. digitatum formed PEE, while other fungal species did not. In contrast to citrus fruit, prenyl methyl ether (PME) was formed as dominant prenyl ether on hazelnuts while only small amounts of PEE were found. PME has not been previously described as volatile metabolite of fungi or as a food-taint. Spiking experiments with deuterated ethanol showed that the ethyl group is likely incorporated into PEE via the aldehyde form. On hazelnuts strongly decayed by P. digitatum yet another prenyl ether was tentatively identified: Prenyl isopropyl ether. Prenyl ethers present a novel group of volatile metabolites of P. digitatum. They are likely typical for this species and have not been described before. Prenyl ethers seem to play a significant role in the smell of food decayed by P. digitatum and should be considered in cases of off-notes and taints.

Synthesis and AChE Inhibitory Activity of Chalcones Mannich Base Derivatives

Chalcone flavokawain A (1) and chalcone prenyl ether derivative 2 were synthesized from naringin, through glycoside hydrolysis, O-methylation or O-prenylation, and base-catalyzed ring-opening reaction. Based on Mannich reaction of chalcone 1 and chalcone prenyl ether derivative 2, fourteen new chalcone Mannich base derivatives 3~16 were synthesized. The aminomethylation occurred preferentially at 3'-C position of chalcones. The structures of all synthesized compounds were determined by MS, NMR and IR spectra. All the synthetic compounds were evaluated for acetylcholinesterase (AChE) inhibitory activity. The results show that chalcone mannich base derivatives 3~5, 9 exhibit good AChE inhibitory activity.

Highly Efficient and Selective Deprotection Method for Prenyl, Geranyl, and Phytyl Ethers and Esters Using Borontrifluoride–Etherate

An efficient, simple, and practical method has been developed for the deprotection of prenyl, geranyl, and phytyl ethers and esters of aromatic and aliphatic compounds using borontrifluoride–etherate (BF3 · OEt2) at room temperature in good to excellent yields for the first time. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.

&lt;strong&gt;Chemosystematics of selected liverworts collected in Borneo&lt;/strong&gt;

The GC/MS analysis of the volatile components present in diethyl ether extracts of 15 Marchantiophyta species collected in Borneo island indicated that each liverwort species, produce own characteristic compounds. Most of the studied species elaborate a large quantity of sesquiterpenoids whereas only a few synthesize monoterpenoids, diterpenoids and aromatic compounds. Sesquiterpenoids, such as herbertanes, gymnomitranes, chiloscyphanes as well as eudesmane, germacrane and guaiane sesquiterpene lactones, can be used as chemosystematics markers. Aromatic compounds like methyl benzoates with prenyl ether group are characteristic of Trichocolea pluma . Diterpenoids belonging to labdane-, clerodane- and fusicoccane-types are chemical markers of Pleurozia gigantea , while cembranes are characteristic for Chandonanthus hirtellus and rearranged 7,8-secolabdane-type diterpenoids for Pallavicinia species. Monoterpenoids, responsible for characteristic fragrance, occur mainly in thalloid liverworts belonging to the order Marchantiales, here represented by Wiesnerella denudata and Dumortiera hirsuta .

Concise Synthesis of Licochalcone A through Water-Accelerated [3,3]-Sigmatropic Rearrangement of an Aryl Prenyl Ether

Claisen-Schmidt condensation of 4-(tetrahydropyran-2-yloxy)acetophenone with 2-methoxy-4-[(3-methylbut-2-en-1-yl)oxy]benzaldehyde gave a THP-protected chalcone ether. Removal of the THP group under mild acidic conditions gave the corresponding chalcone ether, which underwent a water-accelerated Claisen rearrangement under microwave irradiation or heating in a sealed tube in aqueous ethanol to give a good yield of licochalcone A, which has diverse biological activities; no product of deprenylation or abnormal Claisen rearrangement was formed. The abnormal Claisen rearrangement of γ-substituted allyl aryl ethers is known to be a problem in [3,3]-sigmatropic rearrangement reaction; this, however, was not detected in our water-accelerated system.

ChemInform Abstract: Claisen Rearrangement of Prenyl Ethers of Isomeric Acetylnaphthols and Bisprenyl Ethers of 4,6- and 2,4-Diacetylresorcinols.

Claisen rearrangements of the 3-methylbut-2-enyl(prenyl) ethers 3 and 9 of 2-acetyl-1-hydroxyand 1-acetyl-2-hydroxynaphthalenes 1 and 2 and the bis(3-methylbut-2-enyl) ethers 12 and 18 of 2,4-and 4,6-diacetylresorcinols 11 and 17 have been studied under a variety of thermal and catalytic conditions. 2-Acetyl-4-(3- methylbut-2-enyl) naphthalene-1-ol 4 was the sole product on rearrangement of compound 3, in DMA or neat. Under catalytic conditions 3,4-dihydro-2,2-dimethyl-2H-naphtho[1,2-b]pyran 7 was obtained in poor yield. An isomeric pyran, 1,2-dihydro-3,3-dimethyl-3H-naphtho[2,1-b]pyran 10(25–43%) was obtained under both thermal and catalytic conditions from 9. The rearrangement of 12 under thermal conditions (DMA and neat) furnished 3-acetyl-2,4-dihydroxy5-(3-methylbut-2-enyl)acetophenone 13 and 3,8-diisopropylbenzo[1,2-b: 3,4-b′]difuran 14. PdII mediated rearrangement of 12 gave only the partially deprenylated ether, 3-acetyl-4-hydroxy-2-(3-methylbut-2-enyloxy)acetophenone 15(29%). While the isomeric ether 18 gave the monoprenyl ether, 5-acetyl-4-hydroxy-2-(3-methylbut-2-enyloxy)acetophenone 19 in quantitative yield (95%). The rearrangement products were characterised and their formation rationalised in terms of allowed sigmatropic shifts ([3,3] prenyl and [1,5] H) followed by loss of prenyl or acetyl groups. The reactions of prenyl ethers are both comparable to those of the corresponding allyl ethers and consistent with the greater fixed double-bond character of the naphthalene system compared to that of benzene. Prenyl derivatives of benzene and naphthalene containing ortho-hydroxyacetophenone units were formed which have potential in synthesis.

ChemInform Abstract: Remarkable Solvent Effect on Pd(0)-Catalyzed Deprotection of Allyl Ethers Using Barbituric Acid Derivatives: Application to Selective and Successive Removal of Allyl, Methallyl, and Prenyl Ethers.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Remarkable Solvent Effect on Pd(0)‐Catalyzed Deprotection of Allyl Ethers Using Barbituric Acid Derivatives: Application to Selective and Successive Removal of Allyl, Methallyl, and Prenyl Ethers.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Remarkable Solvent Effect on Pd(0)-Catalyzed Deprotection of Allyl Ethers Using Barbituric Acid Derivatives: Application to Selective and Successive Removal of Allyl, Methallyl, and Prenyl Ethers

Pd(0)-catalyzed deprotection of allyl ethers using barbituric acid derivatives in protic polar solvent such as MeOH and aqueous 1,4-dioxane proceeds at room temperature without affecting a wide variety of functional groups. Control of the reaction temperature allows selective and successive cleavage of allyl, methallyl, and prenyl ethers. A study of ligand effects on the deprotection reveals that the improved reactivity in MeOH results from the accelerated oxidative addition to Pd(0).

Total Synthesis of Xanthohumol

The total synthesis of xanthohumol (1) was accomplished in 10% overall yield from phloracetophenone after six steps. Insertion of a prenyl group onto the aryl ring was achieved by a para-Claisen rearrangement after using a Mitsunobu reaction to establish the key prenyl ether precursor. A Claisen-Schmidt condensation was deployed to construct the chalcone scaffold followed by removal of MOM protecting groups under acidic conditions that were optimized to prevent concomitant cyclization to the flavone.