Benzofuran derivatives,effects

A plausible pathway is that the aromatisation of the cyclohexadienone 92 by a proton shift is accelerated in the presence of Ac20 under formation of acetate 93. The simultaneously generated acetic acid then cleaves the acetate to form the free phenol 94 (Scheme 44). This effect was observed for the first time during studies towards the total synthesis of the lipid-alternating and anti-atherosclerotic furochromone khellin 99 [64].The furanyl carbene chromium complex 96 was supposed to react with alkoxyalkyne 95 in a benzannulation reaction to give the densely substituted benzofuran derivative 97 (Scheme 45). Upon warming the reaction mixture in tetrahydrofuran to 65 °C the reaction was completed in 4 h, but only a dimerisation product could be isolated. This... 

Amiodarone (11), a benzofuran derivative, was initially developed as a coronary vasodilator in the early 1960 s [11,12]. Several years later, the efficacy of the compound as an antiarrhythmic agent began to be exploited. The first clinical trials with amiodarone were reported in 1974 [13]. Amiodarone was effective in controlling the tachyarrhythmias of eleven patients with Wolff-Parkinson-White syndrome. Since that time the compound has been studied extensively [14,15]. Recently, in the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial (CAMIAT), amiodarone was shown to reduce mortality during a mean 18 month period following myocardial infarction (13.8% deaths in placebo group vs. 2.1 % deaths in the treatment group) [16]. 

The second alcohol toxin of significance is tremetol, the toxin found in white snakeroot in the midwest and ray less goldenrod in the southwest. Tremetol is an oily extract of the plant and was first associated with the toxic effects, and named appropriately by Couch in 1927. Tremetol is a mixture of methyl ketone benzofuran derivatives, including tremetone, dehydrotremetone, and hydroxytremetone (Beier and Norman, 1990). 

Effect of Heteroelements in Modifying Some Cyclizations — Benzofuran Derivatives Formed by Cyclization of Current Trends in Heterocyclic Chemistry , ed. A. Albert, G. M. Badger and C. W. Shoppee, Academic Press, New York, 1958, pp. 58-64. 

The Pechmann synthesis is unsuitable for acid-sensitive phenols, as for example the furo[2,3 -6]benzofuran derivative (373). An alternative approach uses the enhanced electrophilic character of a vinyl bromide in the presence of zinc carbonate to construct a suitable side-chain adjacent to the phenolic group (71JA746). In the examples cited, ring closure occurred under the mild conditions to form the pyranone ring of the aflatoxins (374). Since neither sodium nor potassium carbonate proved effective, it was considered that chelation of the zinc facilitated the carbon-carbon bond formation (Scheme 115). 

Phenyl benzofuran derivatives, (II), prepared by Miller (3), naphthalene derivatives, (III), prepared by Hamann (4), and 3,4-dihydro-3-aryl-hydroxybenzoxazines, (IV), prepared by Dickson (5) were effective as nonsteroidal androgen receptor modulators and used in the treatment of age-related disorders. 

Sulfur as a heteroatom is apparently free of negative effects, as shown by the thiophen 2 yl derivative 8g, where the enantioselectivity (89% ee, entry 7) was close to that observed for the acetophenone derived imines (Table 4.3). Furan and benzofuran derived imines 8h-8n were reduced with the efficiency laying between that of the sulfur and nitrogen heterocycles (45 77% ee, entries 8 14) the 3 furyl derivative 8m exhibited a significantly higher level of asymmetric induction (77% ee, entry 13) than its 2 furyl isomer 8h (56% and 62% ee at rt and at 20 °C, respectively, entry 8). Again, increasing the steric bulk had a positive effect, as documented by the behavior of the dimethyl derivative 8o (91% ee, entry 15) [12h]. 

Hydroalkoxylation of alkynes, or the addition of alcohol to alkynes, is a fundamental reaction in organic chemistry that allows the preparation of enol ethers and a variety of oxygen-containing heterocycles such as furan, pyran, and benzofuran derivatives. Bergbreiter et al. found that a Mnear poly-(A-isopropylacrylamide) (PNIPAM) polymer exhibited inverse temperature solubility in water (i.e., soluble in cold water but insoluble in hot water). A recoverable homogeneous palladium catalyst was prepared based on the polymer. The PNIPAM-bound Pd(0) catalyst was effective for the reaction of 2-iodophenol with phenylacetylene in aqueous THE media to give the target product... 

Miscellaneous Reactions. Palladium dba has been employed as a catalyst for effecting various annulation reactions. Mediumsized nitrogen heterocycles have been prepared from allenes and amino alkenyl hahdes in the presence of a Pd(dba)2/PPh3 catalyst system. 1,3-Dienes can be converted to benzofuran derivatives upon reaction with o-iodoacetoxy arenes and this reaction has been applied in the synthesis of new coumarins. Dihydro-quinoxalines and quinoxalinones have been obtained via reductive annulation of nitro enamines (eq 26). ... 

As described in Chapter IV, a series of 2-arylbenzofuran derivatives have been isolated from the mulberry tree. Tabcasugi et al. isolated a phytoalexin from diseased mulberry leaves and designated it as chal-comoracin (103) 87). In the course of our studies, three novel 2-aryl-benzofuran derivatives, mulberrofurans C (130), F (131), and G (27), were isolated as hypotensive components. Single intravenous injection of 130, 131, or 27 caused a marked depressor effect in rabbits 111, 112). 

This methodology was later extended by Owen [117] and Nilsson [78] to the employment of o-iodo- and -bromophenols and terminal acetylenes in the presence of stoichiometric amounts of Cu(I) oxide in pyridine or Cu(I) terf-butoxide to generate acetylide 55, allowing the achievement of typically higher or comparable yields (60-82%) of thecorresponding benzofurans 57. Ohemeng [118] and Scammells [119] effectively employed the first catalytic system in the synthesis of biologically active benzofuran derivatives, whereas Nilsson succeeded in the assembly of... 

Lithium salts of o-(alk-2-ynyl)phenols and o-(alk-3-ynyl)phenols (preformed through the reaction of phenols with n-butyllithium at 0 °C) react with iodobenzene, 2-iodothiophene, benzyl bromide, and methyl iodide in the presence of a palladium catalyst to give 2-(alkyli-dene)-3-hydrobenzo[ ]furans (Scheme 12) and 2-(alkylidene)chromanes (Scheme 13), respectively. Both palladium diacetate and palladium dichloride have proved effective catalysts, whereas Pd(dba)2 and PdCl2(PPh3)2/DIBAL-H have given very low yields of the desired products. Minor amounts of isomerized products have been obtained by using palladium diacetate or palladium dichloride and triphenylphosphine whereas the employment of Pd(PPh3)4 has been found to afford only the isomerized benzofuran derivative in low yield. 

We studied the effect of replacing the indole nucleus by other non-basic ring systems and prepared the benzofuran and benzothiophen derivatives by the standard route from the appropriate ketone. It may be seen from Table 7.5 that both derivatives were less active than ondansetron. 

In vitro exposure of chicken trachea cells to 2,3-benzofuran results in substantial inhibition of ciliary activity (Pettersson et al. 1982), which may indicate that ciliotoxicity is involved in the respiratory effects seen in mice. Certain other furan derivatives exhibit pulmonary toxicity due to metabolic activation by lung P-450 oxygenases (Boyd 1981), but 2,3-benzofuran... 

Although alkylbenzofuran derivatives (e.g., 2-methyl-2,3-dihydro-benzofuran) have no vitamin F activity,88 they seem to show some regulating activity on plant growth.89 The 2,2-dimethyl-2,3-dihydro-benzofuran ring is an effective toxophore.90... 

The Shriner-Anderson method consists in the reduction of 3-acetoxy derivatives. 3(2//)-Benzofuranones (237) are heated with Ac20 + NaOAc to give the 3-acetoxy derivative 348, which is hydrogenated (Pt in ethanol) to the benzofuran 349.538 If the reduction is effected on... 

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