3-Methoxy-4-hydroxyphenyl acids

Methoxy-4-hydroxyphenyl Acids The following 3-methoxy-4-hydroxyphenyl acids have been found in normal human urine (A14, A16, S14) (Fig. 11) 3-methoxy-4-hydroxy-... 

The other 3-methoxy-4-hydroxyphenyl acids, as well as a part of the urinary vanillylmandelic acid, arise from dietary precursors their elimination increases markedly, for instance, after ingestion of coflEee (S16). 

Heating a 3-(2-hydroxyphenyl)propionate ester in diphenyl ether with palladium-charcoal induces a combined cyclization and dehydrogenation [3437], Simultaneous de-O-benzylation and cyclization of a 2-(benzyloxy)acrylic acid by heating with acetyl chloride containing phenyltrimethylammonium iodide gives good yields of a fused pyran-2-one [3836]. In contrast, an o-methoxy-benzylidenemalonic acid (as its potassium salt) cyclizes in the cold when treated with trifluoroacetic acid-trifluoroacetic anhydride [3938]. 

Chemical Name 7-( (Carboxy(4-hydroxyphenyl)acetyll amino] 7-methoxy-3-[ [ (1-methyl-1 H-tetrazol-5-yl)thio] -methyl] -8-oxo-5-oxa-1 -azabicycio [4.2.0] oct-2-ene-2-carboxylic acid disodium salt... 

To a solution of 7 (d-p-hydroxyphenyl-0i-carboxyacetamido-7(l-methoxy-3-(1-methyl-tetrazol-5-vl)thiomethyl-1-oxadethia-3-cephem4-carboxylic acid (359 mg) in methanol (7 ml) is added a solution of sodium 2-ethylhexanoate in methanol (2 mols/liter 1.73 ml) at room temperature. After stirring for 10 minutes, the reaction mixture is diluted with ethyl acetate, stirred for 5 minutes, and filtered to collect separated solid, which is washed with ethyl acetate, and dried to give disodium salt of 7 (a-p-hydroxyphenyl-a-carboxyacetamido)-7Q -methoxy-3-(1-methyl-tetrazol-5-vl)thiomethyl-1-oxadethia-3-cephem4-carboxylic acid (342 mg). Yield 885%. Colorless powder. MP decomposition from 170°C. 

As compounds exhibiting enhancing effects on CL reactions, a variety of phenols, e.g., firefly luciferin and 6-hydroxybenzothiazole derivatives [12,13], 4-iodophe-nol [14], 4-(4-hydroxyphenyl)thiazole [15], 2-(4,-hydroxy-3 -methoxy-benzyli-dene)-4-cyclopentene-l,3-dione (KIH-201) [16], and 2-(4-hydroxyphenyl)-4,5-diphenylimidazole (HDI) and 2-(4-hydroxyphenyl)-4,5-di(2-pyridyl)imidazole (HPI)[17] (Fig. 6A), and phenylboronic acid derivatives, e.g., 4-phenylylboronic acid [18], 4-iodophenylboronic acid [19], and4-[4,5-di(2-pyridyl)-l //-imidazol-2-yl]phenylboronic acid (DPPA) [20] (Fig. 6B), in the luminol/hydrogen peroxide/peroxidase system are well known. Rhodamine B and quinine are used as sensitizers in the CL-emitting reaction between cerium (IV) and thiol compounds. This CL reaction was successfully applied to the sensitive determination of various thiol drugs [21-32],... 

Figure 6 Representative (A) phenol-type and (B) phenylboronic acid-type enhancers for luminol/hydrogen peroxide/peroxidase system. KIH-201, 2-(4 -hydroxy-3 -methoxy-benzylidene)-4-cyclopentene-1,3-dione HDI, 2-(4-hydroxyphenyl)-4,5-diphenylimida-zole HPI, 2-(4-hydroxyphenyl)-4,5-di(2-pyridyl)imidazole DPPA, 4-[4,5-di(2-pyridyl)-lH-imidazol-2-yl]phenylboronic acid).

The phenols (no. 30a, 30b, 32) are used as reactants to synthesize several of the company s products, including the benzotriazoles. The 2-chloro-4,6-bls-isopropylam-ino-s-triazine (no. 13) are herbicides the chloro compound is used to control weeds and grass in corn and in milo, and the methoxy compound is used for general plant control. Several esters of 3-(3 ,5 -di-t-butyl-4 -hydroxyphenyl) propionic acid were identified, the most abundant being the octadecyl and methyl esters. 

The BBrs reaction with 1. l-dimethoxy-2.4.6-di-tert-butyl-4-(4 -methoxyphenyl)-X -phosphorin 200 leads to cleavage of both methoxy groups in addition to the methoxy group at the phosphorus, the 4 -methoxy group is attacked. The 2-hydro-4-(4 -hydroxyphenyl)-phosphinic acid methyl ester 201 can be methylated with methyl iodide in methanol/sodium methylate at the phenolic group, leading to 202, which can also be prepared by hydrogen peroxide oxidation of 2.6-di-tert-butyl-4-(4 -methoxy phenyl)-X -phosphorin 204 to 203, followed by diazomethane methylation (see Table 13, p. 61). 

Lewis acids have also been found to promote the electrophilic cleavage of cyclobutanes. The key feature of this reaction can be depicted by the conversion of the chiral 4-(2-hydroxy-6-methoxyphenyl)-6,6-dimethylbicyclo[3.1.1]heptan-2-ones 5 and 4-(2-methoxy-6-hydroxyphenyl)-6,6-dimethylbicyclo[3.1.1]hept-3-en-2-ones 7 to (6a5, 10a/ )-(-)-l-methoxy-6,6a,7,8,10,10a-hexahydro-6,6-dimethyl-9//-dibenzo[b,c/]pyran-9-ones 6 and (6aS)-( + )-methoxy-6,6a,7,8-tetrahydro-6,6-dimethyl-9//-dibcnzo[b//]pyran-9-ones 8, respectively, on treatment with either tin(IV) chloride in chloroform or with aluminum trichloride in dichloromethane.52... 

Fmoc-amino acids used as building blocks of testing compounds are as follows Fmoc-Asp(OtBu)-OH, Fmoc-Cys(Trt)-OH, Fmoc-Asn(Trt)-OH, Fmoc-Gln(Trt)-OH, Fmoc-Met-OH, Fmoc-Glu(OtBu)-OH, Fmoc-Lys (Boc)-OH, Fmoc-Ile-OH, Fmoc-His(Trt)-OH, Fmoc-Tyr(tBu)-OH, Fmoc-Arg(Pmc)-OH, Fmoc-Phe-OH, Fmoc-Ser(tBu)-OH, Fmoc-Thr(tBu)-OH, Fmoc-Val-OH, Fmoc-Pro-OH, Fmoc-Trp(Boc)-OH, Fmoc-D-Ala-OH, Fmoc-D-Arg(Pmc)-OH, Fmoc-D-Trp(Boc)-OH, Fmoc-D-Cys(Trt)-OH, Fmoc-D-Asp(OtBu)-OH, Fmoc-D-Glu(OtBu)-OH, Fmoc-D-His(Trt)-OH, Fmoc-D-Gln(Trt)-OH, Fmoc-D-Leu-OH, Fmoc-D-Met-OH, Fmoc-D-Pro-OH, Fmoc-D-Ser(tBu)-OH, Fmoc-D-Lys(Boc)-OH, Fmoc-D-Tyr(tBu)-OH, Fmoc-D-Thr(tBu)-OH, Fmoc-D-Phe-OH, Fmoc-D-Asn(Trt)-OH, Fmoc-3-(4-pyridyl)alanine, Fmoc-D-3-(3-pyridyl)alanine, Fmoc-4-tert-butoxyproline, Fmoc-3-chlorophenylalanine, Fmoc-norleucine, Fmoc-2-cyclohexylglycine, Fmoc-2-aminoisobutyric acid, Fmoc-tranexamic acid, Fmoc-(i ,S)-3-amino-3-(2-furyl)propionic acid, Fmoc-(i ,S)-(6,7-di-methoxy)-l,2,3,4-tetrahydroquinoline-3-carboxylic acid, Fmoc- (R, S)-3-amino-3-(4-hydroxyphenyl)propionic acid, Fmoc-(i ,S)-3-aminovaleric acid, Fmoc-(i ,5 )-3-amino-3-(3,4-dichlorophenyl)propionic acid, Fmoc-isonipecotic acid, Fmoc-(i ,S)-3-amino-3-(3,4-methylenedioxyphenyl)... 

A 3-amino-/V-[2-chloro-4 [(3-hydroxyphenyl)methyl]aminocarbonyl benzoyl-L-alanine substituted Wang resin was /V-acylated with 2-methoxy-11-oxo-l l/7-pyrido[2,l-Z>]-quinazoline-8-carboxylic acid in A-methylpyrro-lidone in the presence of l-hydroxy-7-azabenzotriazole and diisopropylcar-bodiimide (00MIP2). The product was cleaved from the resin by treatment with 50% TFA in a mixture of CH2C12 and MeOH. 

OXA-AZABICYCLO(4.2.0)OCT-2-ENE-2-CARBOXYLIC ACID, 7-(2-CARBOXY-2-(p-HYDROXYPHENYL)ACETAMIDO)-7-METHOXY-3-(((1-METHYL-1H-TETRAZOL-5-... 

The zizyphine-A type are 13-membered cyclopeptides composed of / -(2-methoxy-5-hydroxyphenyl)vinylamine, 3-hydroxyproline, and another amino acid. The first known representative was described as zizyphine in 1965 and given an open chain structure (13). It was subsequently renamed zizyphine-A in view of a further examination of Zizyphus oenoplia which disclosed other peptide alkaloids (14). 

Under a nitrogen blanket, a mixture of 3 g of 4-(2-piperidinoethoxy)benzoic acid hydrochloride, 2 drops of dimethylformamide, 2.5 ml of thionyl chloride and 40 ml of chlorobenzene was heated at 70°-75°C for about one hour. The excess thionyl chloride and 15-20 ml of solvent were then distilled off. The remaining suspension was cooled to ambient temperature, and to it were added 100 ml of dichloromethane, 2.7 g of 6-methoxy-2-(4-methoxyphenyl) benzo[b]thiophene and 10 g of aluminum chloride. The solution was stirred for about one hour, 7.5 ml of ethanethiol was added, and the mixture was stirred for 45 minutes more. Then 40 ml of tetrahydrofuran was added, followed by 15 ml of 20% hydrochloric acid, with an exotherm to reflux. Fifty ml of water and 25 ml of saturated aqueous sodium chloride was added. The mixture was stirred and allowed to cool to ambient temperature. The precipitate was collected by filtration and washed successively with 30 ml of water, 40 ml of 25% aqueous tetrahydrofuran, and 35 ml of water. The solids were then dried at 40°C under vacuum to obtain 5.05 g of product, which was identified by NMR as 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl] benzo[b]thiophene hydrochloride melting point 217°C. 

C) N-Methyl-(3-methoxy-4-hydroxyphenyl)-alanine (III).—In a 2-1. round-bottomed flask (Note 5), 18 g. (0.07 mole) of the crude reduction product is refluxed for twelve hours with a solution of 180 g. of crystalline barium hydroxide in 270 cc. of water. The hot solution is diluted with 1.2 1. of water, and the barium is precipitated by addition of 250-270 cc. of 6 N sulfuric acid (Note 6). The precipitated barium sulfate is separated by centrifuging and washed with two 100-cc. portions of water the combined water solutions are evaporated under reduced pressure at 50° to a volume of about 50 cc. The acid solution is made alkaline to litmus by addition of about 10 cc. of a 12 per cent solution of ammonium hydroxide in water. After standing for twenty-four hours at 0°, the mixture is filtered, and the solid is washed with cold water and dried. The yield is 12 g. (74 per cent of the theoretical amount) (Note 7). On rapid heating, the solid melts at 273-275°. When recrystallized from water, the substance melts at 276-278°. The crude product may be used for the next step. 

N,N -BIS(1,1-DIMETHYLETHYL)-1,2-ETHANEDIAMINE see DEClOO 3-((3,5-BIS(l,l-DIMETHYLETHYL)-4-HYDROXYPHENYL)METHYLENE)-l-METHOXY-2-PYRROUDINONE see MELIOO ((3,5-BIS(l,l-DLMETHYLETHYL)-4-HYDROXYPHENYL)METHYL)PHOSPHONIC ACID, MONOETHYL ESTER, NICKEL(2+) SALT (2 1) see BJK560... 

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