3,4-Methylenedioxyphenyl group

The distinctive feature from alkamides isolated from Piperaceae family is the presence of an aromatic ring, commonly a 3,4-methylenedioxyphenyl group (although p-methoxyphenyl and 3,4,5-trimethoxyphenyl have also been found) linked to the end of an unsaturated C3-C16 fatty acid chain [20]. The amine group commonly found is an A-isobutyl, pyrrolidinyl, or piperidinyl group. Fig. 4 [21-23]. 

Bowman, M,C, and Beroza, M, 1967). Spectra and analyses of insecticide synergists and related compounds containing the methylenedioxyphenyl group hy xpectro-pbolofluoromelry (SPF) and spectrophotophn.sphorimelrv (SPP). Residin Rev. 17, 1-22. 

In the biosynthesis of the characteristic methylenedioxyphenyl group a decisive role is attributed to the oxenium ion, which is formed from the properly substituted... 

The H-NMR, 13C-NMR, and LL1 COSY spectra revealed the presence of the same partial structures as in 104, a phenyl group, a 3-methoxy-4,5-methylenedioxyphenyl group, a trisubstituted double bond, and two acetoamides. The spectra also indicated the presence of a -CH2-CH-CH2- moiety. These partial structures were connected from the COLOC spectrum, and the whole structure of 105 was determined to be 1,4-diacetyl-2-benzyl-5-(3-methoxy-4,5-methylenedioxybenzyl)-... 

Whereas many of the Piper amides, particularly those embodying the methylenedioxyphenyl group, are relatively stable, a number of the aliphatic unsaturated compounds, for example pellitorine, 5, have been reported to be very unstable [4, 56, 81, 127]. The propensity of cinnamic and piperic acid amides to undergo light-promoted E/Z isomerism has been noted, and dictates caution in drawing conclusions concerning the stereochemical composition of related naturally-occurring material [6]. 

Five amides, 50(n=4,6), 55, 5 and 6(n=6), isolated from P. guineense were investigated by Candy and co-workers [10] with respect to their knockdown and lethal activity against adult houseflies, as well as the rates of recovery of M. domestica from the effects of sublethal doses of the amides. As with other insecticides, rapid and potent knockdown activity on topical application of the amides depends, apart from the intrinsic toxicities of the individual compounds, on their ability to penetrate the cuticle and relevant membranes en route to the site of action. Attempts to correlate knockdown activity in the P. guineense amide series with polarity on this basis seemed to show some inconsistencies, perhaps as a result of steric factors [10,102]. The rate of recovery from the effects of sub-lethal doses of insecticides is associated, inter alia, with processes that lead to removal of the toxicant, so that recovery from treatment with Piper amides embodying the methylenedioxyphenyl group, which retards the action of mixed function oxidases, is slower than recovery from the effects of the less stable aliphatic amides. 

A striking illustration of the effect of chemical structure on insecticidal properties is provided by the data given in this paper on compounds related to piperonyl butoxide. According to the above theory, the methylenedioxyphenyl nucleus present in this substance is the toxophore. The materials selected for comparison show the reduction in toxicity produced, first, by modifying the toxophore, and, second, by substituting different groups for the auxotox radical. 

The stereoselective intramolecular Henry reactions have been reported by Seebach. The Michael addition of doubly deprotonated acetyl acetaldehyde to l-methylenedioxyphenyl-2-nitroethene followed by subsequent intramolecular nitro-aldol cyclization leads to the diastereomerically pure cyclohexanone derivative, where the nitro and OH groups are cis as shown in Eq. 3.73.114 This reaction is applied to the synthesis of l-desoxy-2-lycorinone as shown in Eq. 3.74.115... 

R = Me) under standard generation conditions, in the presence of activated alkene dipolarophiles led to the expected adducts (Scheme 3.49). In the case of trans-l-nitro-2-(3,4-methylenedioxyphenyl) ethene, a 3 2 mixture of diastereoisomers was isolated. Replacement of the methyl group with a methyl ether (R = CH20Me),... 

Certain methylenedioxyphenyl compounds such as safrole (84) bind to and inhibit cytochrome P450, probably via interaction of a carbene formed from the methylene group and... 

The final group of natural benzofurans includes the 2-phenylbenzo-furans and 2-phenyl-2,3-dihydrobenzofurans. 2-(6-Hydroxy-2-methoxy-3,4-methylenedioxyphenyl)benzofuran (64)147 has recently been isolated from yeast. Other members of the same group recently isolated from various plants are eupomatene (7-methoxy-3-methyl-2-(3,4-methylene-dioxyphenyl)-5-fi-Gms-propenylbenzofuran (65) 180 egonol (66),147,181-184... 

The structure of MDA can be viewed as an aromatic ring (the 3,4-methylenedioxyphenyl ring) with a three carbon chain sticking out from it. The amine group is on the second of the three carbon atoms. The isomers, with the amine function moved to the first of these carbons atoms (a benzylamine) and with the amine function moved to the third (furthest out atom) of these carbon atoms (a (n)-propylamine), are known and both have been assayed. 

The triethylamine salt of 2,2-dimethyl-3-(3,4-methylenedioxyphenyl)-propionic acid (5.4 g amine, 11.4 g acid) was dissolved in 10 mL 11,0 and diluted with sufficient acetone to maintain a clear solution at ice-bath temperature. A solution of 6.4 g ethyl chloroformate in 40 mL acetone was added to the 0 °C solution over the course of 30 min, followed by the addition of a solution of 4.1 g sodium azide in 30 mL H20. Stirring was continued for 45 min while the reaction returned to room temperature. The aqueous phase was extracted with 100 mL toluene which was washed once with H20 and then dried with anhy drou s Mg S04. Thi s org ani c sol uti on of the azide was heated on a steam bath until nitrogen evolution had ceased, which required about 30 min. The solvent was removed under vacuum and the residue was dissolved in 30 mL benzyl alcohol. This solution was heated on the steam bath overnight. Removal of the excess benzyl alcohol under vacuum left a residue 13.5 g of l-(N-(benzyloxycarbonyl)amino)-1,1 -dimethyl-2-(3,4-methylenedioxyphenyl)ethane as an amber oil. The dimethyl group showed, in the NMR, a sharp singlet at 1.30 ppm in CDCH,. Anal. (C19H2lN04) C,H. This carbamate was reduced to the primary amine (below) or to the methylamine (see under MDMP). 

A related approach exploited a A-cyanomethyl group to serve in the dual role of a nitrogen protecting group and a latent precursor of the formaldehyde im-inium ion (e.g., 478), and this innovative modification in tactics resulted in a simplified route to the c/.v-3a-aryloctahydroindole 474 (203a,c). To this end, the amino ketone 482 was readily prepared in one step by the reaction of 1,2-bis(trimethylsilyloxy)cyclopentene with A -benzyl-A -cyanomethyl amine. When 482 was exposed to [l-(3,4-methylenedioxyphenyl)ethenyl]lithium, a mixture (1 14) of 483 and 484 was obtained. It is noteworthy that the stereochemical sense... 

Sometimes 2-amino alcohols, the hydroxyl group of which is not primary, can still give thiazolidine-2-thiones (LX). An instance of this is isopropanolamine which yields a mixture of 5-methylthiazolidine-2-thione and 5-methyloxazolidine-2-thione 172. Others are l-phenyl-2-aminoethanol and 1-(3,4-methylenedioxyphenyl)-2-aminoethanol, from which only the thiazolidine-2-thiones are obtained when the reaction is carried out in basic medium. 

The arylbenzofurans are marginally more common than isoflav-3-enes but they still constitute an unusual and infrequently occurring group of isoflavonoids. Cicerfuran (2-(2 -methylenedioxyphenyl)-6-... 

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