Isocoumarins

Coumarins and Isocoumarins.—Ketene intermediates have been detected at — 190 °C during the photocyclization of 2,6-dichIoiocinnamates to 5-chlorocou-marins. 

A convenient and efficient route to isocoumarins has been described starting from readily available substituted indan-l-ones, which are first converted to the enol form with trifluoroacetic anhydride, then cleaved with ozone. Isocoumarin-4-carboxylic acid is easily prepared from homophthalic acid by addition of Vilsmeier reagent followed by hydrolysis. 

Cyclization of the unsaturated epoxy-ester (100), to a-pyrone (101), has been effected using iodine and toluene-p-sulphonic acid in benzene.  

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The isocoumarin 151 is prepared by the intramolecular reaction of 2-(2-propenyDbenzoic acid (149) with one equivalent of PdCbjMeCN) . However, the (Z)-phthalide 150 is obtained from the same acid with a catalytic amount of PdjOAc) under 1 atm of Oi in DMSO, alone is remarkably efficient in reoxidizing Pd(0) in DMSO. The isocoumarin 151 is obtained by the reaction of 2-(l-propenyl)benzoic acid (152) under the same conditions[4], 2-Vinylbenzoic acid (153) is also converted into the isocoumarin 154, but not to the five-membered lactone) 167,170],... 

Aryl- or alkenylpalladium comple.xcs can be generated in situ by the trans-metallation of the aryl- or alkenylmercury compounds 386 or 389 with Pd(Il) (see Section 6). These species react with 1,3-cydohexadiene via the formation of the TT-allylpalladium intermediate 387, which is attacked intramolecularlv by the amide or carboxylate group, and the 1,2-difunctionalization takes place to give 388 and 390[322]. Similarly, the ort/trt-thallation of benzoic acid followed by transmetallation with Pd(II) forms the arylpalladium complex, which reacts with butadiene to afford the isocoumarin 391, achieving the 1,2-difunctionalization of butadiene[323]. 

Phytoalexins are low molecular weight compounds produced in plants as a defense mechanism against microorganisms. They do, however, exhibit toxicity to humans and other animals in addition to microbes (30). Coumarins, glycoalkaloids, isocoumarins, isoflavonoids, linear furanocoumarins, stilbenes, and terpenes aU. fall into the category of phytoalexins (31). Because phytoalexins are natural components of plants, and because their concentration may increase as a response to production and management stimuli, it is useful to recogni2e the possible effects of phytoalexins in the human diet. 

Homofolic acid, 5,11-methenyl-tetrahydro-biological activity, 3, 327 Homofolic acid, tetrahydro-biological activity, 3, 327 Homoisoflavanones occurrence, 3, 722 thermoisomerization, 3, 722 thermolysis, 3, 728 Homolytic reactions heterocyclic compounds reviews, 1, 74 Homophthalic acid isocoumarins synthesis from, 3, 830 synthesis, 3, 830 Homophthalic anhydride isochroman-l-one synthesis from, 3, 860 20a-Homoporphyrin nomenclature, 1, 30 Homopterocarpin isolation, 4, 998 ( )- D- Homotestosterone synthesis, 1, 453 Homer-Emmons reaction chromene synthesis by, 3, 749 Hortiacine isolation, 3, 149 Hortiamine isolation, 3, 149... 

Isobenzofuranone — see Phthalides, 552 Isobenzopyrylium salts isocoumarin synthesis from, 3, 834 synthesis, 3, 862, 863, 867, 868 Isobenzopyrylium salts, l-amino-3-aryl-synthesis, 3, 867 Isobenzopyrylium salts, 1-aryl-NMR, 3, 592... 

Isocoumarin, 3,4-dihydro- — see Isochroman-l-one Isocoumarin, 8-hydroxy-3-methyI-occurrence, 3, 677 Isocoumarin, 8-methoxy-3-methyI-reactions... 

Isocoumarin-3-carboxyIic acid, 8-methoxy-synthesis, 3, 834 Isocoumarin-4-carboxylic acid methyl ester synthesis, 3, 832... 

Isocoumarin-3,4-dicarboxylic acid diethyl ester hydrolysis, 3, 691 Isocoumarins... 

Isoquinol-4(l H)-one, 2,3-dihydro-synthesis, 2, 73 Isoquinolinones from isocoumarins, 3, 691 magnetic circular dichroism, 2, 129 synthesis,... 

Iso-crotonsaure, /. isocrotonic acid, -cumarin, n. isocoumarin, isocumarin. -cyansaure, /. isocyanic acid, -cyanursaure, /. isocyanuric add. 

Diels-Alder cycloaddition of 3,4-bis(trifluoromethyl)furan with ethyl propynoate involved addition of two a,/3-unsaturated esters followed by acid-catalyzed ring opening, rearrangement, and elimination of ethanol to give a 6,7-bis(trifluoromethyl)isocoumarin-3-carboxylate [92JFC(56)359]. 

Irradiation of mixtures of 2-methylbenzoyl cyanide and benzoyl cyanide results in the exclusive formation of the mixed cycloadduct, from which elimination of HCN leads to isocoumarins <96CJC221>. 

The acyl-enzyme can eliminate the 4-chlorine atom to generate this reactive intermediate that can then react with a nearby nucleophile such as His57 to give an alkylated acyl-enzyme derivative in which the inhibitor moiety is bound to the enzyme by two covalent bonds (Scheme 11.5). Inhibition is irreversible.59 The mechanism has been confirmed by X-ray structural analysis of protease-isocoumarin complexes. There is a cross-link between the inhibitor and the Serl95 and His57 residues of PPE.60 Human leukocyte elastase is also very efficiently inactivated.61... 

Kerrigan, J. E. Oleksyszyn, J. Kam, C.-M. Selzler, J. Powers, J. C. Mechanism-based isocoumarin inhibitors of human leucocyte elastase. Effects of the 7-amino substituent and the 3-alkoxy group in 3-alkoxy-7-amino-4-chloroisocoumarins on inhibitory potency. j. Med. Chem. 1995, 38, 544-552. 

Bihel, F. Quelever, G. Lelouard, H. Petit, A. Alves de Costa, C. Pourqie, O. Checler, F. Thellend, A. Pierre, P Kraus, J.-L. Synthesis of new 3-alkoxy-7-amino-4-chloro-isocoumarin derivatives as new beta-amyloid peptide production inhibitors and their activities on various classes of protease. Bioorg. Med. Chem. 2003, 11, 3141-3152. 

Solid extracts of (1) alfalfa and (2) red clover (used in food flavorings) were examined by GC/MS. 389 of 450 detected components were identified in (1), vs. 210 of 309 components detected in (2). In both extracts, predominant compounds identified were esters (1) 105, (2) 55 acids (1) 42, (2) 31 alcohols (1) 34, (2) 31 and hydrocarbons (1) 28, (2) 14. Many other compounds were also found, including cannabinol, caffeine, scopolamine, isocoumarin, phenylpentadienal, phenylhexadiene, and nepetalactone.25... 

Camponotus rufipes W-HG Trail following 3,4- Dihydro - 8 -hydroxy- 3,7- dim e thyl-isocoumarin 120 [167]... 

Camponotus silvicola W-HG Trail following (3R)-(-)-3,4-Dihydro-8-hydroxy-3,5,7-trimethyl-isocoumarin 121 [167]... 

The benzo analogues otherwise named triazino[5,6- )isocoumarines 195, were prepared by the cyclization of 175 with DCC (92CCCI23). 

The choice of catalyst controls the intramolecular cyclisation of 2-(l-alkynyl)benzoic acids, with AgNCh effecting efficient formation of 3-substituted isocoumarins, but Ag powder favouring a 5-exo-dig-cyclisation to the phthalide (Scheme 45) <00T2533>. 

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