Methoxybenzoyl derivatives

For fibrinolytic studies the methoxybenzoyl derivative of r-tPA with a deacylation half-time of IQ minutes was chosen. Its fibrinolytic activity, which had been lost during acylation, was completely recovered by dcacylation. This was Hfninnatwitiirf fay the release of radioactivity from 1KI-labeled plasma dots, In these experiments r-tPA and the methoxybenzoyl derivative were found to possess the same fibrinolytic activity (Fig. 13). 

Ketene elimination from azolides on electron impact gives rise to molecular ions of the corresponding unsubstituted azoles. Al-Acetylimidazoles lose CO, but the [M — CO] ions do not have JV- or C-methylazole structures. In a study of 2-aroylazoles Lim " has shown that a hydrogen radical is commonly lost from the molecular ion CO loss from both the M and [M — 1] species is characteristic p-methoxybenzoyl derivatives lose either formaldehyde or CH3 followed by CO from the [M — 29] fragment. 

Anisoylatedplasminogen streptokinase activator complex (APSAC)(Table 11-4) is an anisoyl (p-methoxybenzoyl) derivative of the active (lysine) site of the plasminogen component of this complex. Acylation inactivates the enzyme but does not decrease the affinity of the complex for fibrin. The resultant slow deacylation (tU2 = 40 min) should achieve relative selectivity for the fibrin in the clot over circulating plasma fibrinogen. Hydrolysis of anisoyl amide following binding onto the thrombus (i.e., activation) leads to fibrinolysis. APSAC has been reported to produce a 60-80% reperfusion rate following IV administration. 

Chlorophenyl)-5-(4-methoxyphenyl)isoxazole has also been prepared from the dilithio derivative of 4-ehloroacetophenone oxime by two other methods (a) reaction with anisonitrile (4-methoxybenzoni-trile) followed by acid-catalyzed cyclization8 and (b) condensation of anisolyl chloride (4-methoxybenzoyl chloride) followed by acid-catalyzed cyclization. ... 

The Wittig reaction, or its phosphonate modification, can be a very useful reaction in the synthesis of anomerically functionalized precursors to C-nucleosides, particularly when the ring-closure reaction leads to five-membered, anhydro derivatives, and occurs with a high degree of stereocontrol. Zhdanov and coworkers,130 showed that the following five-membered, Wittig products (179-182) were formed from various free sugars and (p-methoxybenzoyl)- and (acetyl-methylene)-triphenylphosphoranes. 

Forty new compounds have been reported in this class during the last 12 years. Many references concerned the well-known O-acetyl, O-caffeoyl, O-p-coumaroyl, and O-feruloyl esters. The p-hydroxybenzoyl and p-methoxybenzoyl groups gave rise to two new natural 6"-0-acylated isoorientin derivatives in Polygonum perfoliatumin A and B. 

In the same manner as for l-(2-alkylbenzoyl)-2-(methoxymethyl)pyrrolidines 8 (vide supra), Birch reduction-alkylation of pyrrolobenzoxazepinones, e.g., 1. gives mainly the a-alkylation products (see Table 6)26,2R u. The chemical yields and diastereoselectivities are usually excellent, except for alkylation with iodomethane when the diastereoselectivity is moderate26. The facial selectivity is opposite to that observed upon direct Birch reduction-alkylation of the ortho-methoxy derivatives, i.e., 2-alkoxymethyl-l-(2-methoxybenzoyl)pyrrolidines (vide supra). 

The reaction of anisoyl chloride (p-methoxybenzoyl chloride) with hexachlorophene (HCP) produces a derivative which can be detected in nanogram quantities by HPLC with UV detection [51]. The reaction product is the dianisate ester 2,2 -methylenebis(3,4,6-trichlorophenylp-methoxybenzoate). 

An alternative method for asymmetric and metal-free sulfoxidation was explored by Kita et al. [133], In their approach, iodosylbenzene (Ph-I02) was used as oxidant in reversed micelles formed by cetyltrimethylammonium bromide (CTAB) in toluene. From the numerous chiral inductors tested, tartaric acid derivatives proved best. In the presence of 10 mol% bis(2-methoxybenzoyl)tartaric acid, methyl (4-nitrophenyl)sulfide was converted into the sulfoxide in 91% yield and with 72% enantiomeric excess [133],... 

Anhydro-C-(p-methoxyphenyl)aldoses and anhydro- 1,3-dideoxy-ketoses were found to be compounds usually produced on heating free and partially protected aldoses with p-methoxybenzoyl- and acetyl-methylenetriphenylphosphoranes, respectively, in N,N-di-methylformamide. Many of them were isolated by thin-layer chromatography on alumina, although, on several occasions, these compounds were available only as mixtures of the five- and six-membered anhydro derivatives, because of their similar chromatographic mobilities. Five-membered anhydro derivatives are favored, but exclusive formation of six-membered anhydro derivatives was observed when five-membered ring-closure was impossible. Only L-rhamnose on reaction with acetylmethylenephosphorane formed a six-membered derivative, 196b. 

Coupling of glycolaldehyde with (p-methoxybenzoyl)methylene-triphenylphosphorane produced7 8 an unexpected product having electronic and infrared spectra similar to those of p-methoxyaceto-phenone. This compound was readily converted into the furan derivative 199b and may, therefore, be the cyclopropane derivative... 

Reactions of substituted bis(3-aIkoxybenzoyl) peroxides in neat phenols afford mainly 8-alkoxy-677-dibenzo[fc, d]pyran-6-ones and orf/zo-benzoyloxylation products of the phenol. For example, bis(3,4-dimethoxybenzoyl) peroxide (561) in neat p-methylphenol was completely decomposed in 1 h at 60 °C with the formation of a dibenzo-a-pyrone derivative 562 (60%) together with an ortho-ortho coupled product 563 (21%) and benzoate 564 (5%). In contrast, dibenzoyl peroxides having no mefa-electron-releasing substituents gave mainly ort/zo-benzoyloxyphenols. For example, decomposition of bis(4-methoxybenzoyl)... 

Evidence for carbene intermediates has been obtained from the reactions of o/Y//o-substituted aroylphosphonates such as 2-methoxybenzoyl-, 2-ethylbenzoyl-, and 2-phenylbenzoylphospho-nates. They undergo an insertion of the carbene into a C-H bond with the formation of dihydroben-zofuran or indan derivatives. The reaction is accompanied by the formation of ylide in a temperature-dependent manner. 

In the other synthetic route (119), Birch reduction-alkylation and transformation of functionalized hexahydroindoline derivatives constitute key reactions (Schemes 4 and 5). Birch reduction of A-(2-methoxybenzoyl)-(25)-methoxymethylpyrrolidine, followed by alkylation with 2-acetoxyethyl bromide, produced a key compound 76, azidation of which, followed by hydrolysis with acid, gave the azide 77 in 69% yield (two steps). lodolactoni-... 

Derivatives are monomarc, 3-benzoyl-3-(4-chlorophenyl)-l,l-dimethylurea (34) phenobenzuron, 3-bcnzoyl-3-(3,4-dichlorophenyl)-l,l-dimethylurea (35) and methoxymarc, 3-(4-methoxybenzoyl)-3-(4-chlorophenyl)-1,1 -dimethylurea (36). 

Dimethyl [a-(hydroxyimino)benzyl]phosphonate is stable in mineral acid but decomposes in formic acid containing formate with the liberation of benzonitrile, but otherwise the behaviour is different from that in boiling acetic acid when an additional product, a phosphoramidate ester, is obtained by a Beckmann rearrangement. For the oximes of the (4-methoxybenzoyl)- or (4-chlorobenzoyl)-phosphonic esters, only the phosphoramidate diester 127 is obtained, but for all the substrates examined [additionally the unsubstituted benzoyl- as well as the (4-methylbenzoyl)phosphonic derivatives], the formation of the phosphoramidate ester demonstrates a high migratory aptitude of the phosphinoyl group (Scheme 22) ... 

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