3- Amino-4- isocoumarins

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... 

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. 

Isocoumarins inactivate many serine proteases. For example, 7-amino-4-chloro-3-methoxyisocoumarin acylates serine 195 of elastases as follows.s... 

Isocoumarins react with aqueous ammonia or alkylamines to give good yields of isoquinolin-l-ones for example 3-(4-methoxyphenyl)-l,2-dihydroisoquinolin-l-one (282). A 7-nitro group in the isocoumarin may be reduced by treatment with hydrazine and Raney nickel to the corresponding 7-amino derivative (284), but with hydrazine alone a 2,3-benzodiazepin-l-one (283) is formed (68JCS(C)2205,57JGU2342,81CPB249). 

Formylbenzoic acid, potassium cyanide and anilines react in the presence of acetic acid to afford 3-amino-4-arylamino-isocoumarins (Scheme 215). The reaction proceeds via an initial Strecker reaction to form intermediate 786 followed by intramolecular attack of the carboxyl group onto the nitrile (Scheme 215) <2005EJ0817>. 

WAS) in Aspergillus oryzae. Initially, the expression strain produced the isocoumarin 38, which indicated that WAS is a heptaketide synthase (Fig. 2b). It was then realized that the expression construct used in this experiment had a deletion that resulted in the expressed WAS missing the final 67 amino acids of the C-terminal TE domain. When the complete wA gene was expressed, however, the heptaketide naphthopyrone YWAl 39 was produced (10). A series of experiments that involve step-wise shortening of the C-terminus of WAS showed that deletion of as few as 32 amino acids resulted in production of the isocoumarin 38. Site-directed mutagenesis of a conserved... 

Substituted isocoumarins 27 result from the reaction of 2-iodobenzoic acids with terminal alkynes in ethanol under combined Pd/Cu catalysis <05JOC4778> and a one-pot reaction between 2-formylbenzoic acid, substituted anilines and KCN in AcOH initiated by a Strecker reaction affords good yields of 3-amino-4-(arylamino)isocoumarins (Scheme 10) <05EJO817>. 

Silver nitrate. 18,320 19, 305-306. j Cyclization. 2-AlkynylbenzoK Substituted isocoumarins are the majo Carbonyl compounds from t the a-amino nitrile derivatives of enal drolysis of the products. ... 

The iron-catalyzed synthesis of dihydro-2H-pyrans, 2H- and 4H-chromenes, chromones, isocoumarins and xanthenes were described in a broad review on the synthesis of heterocycles (14T4827), while the synthesis of 2H-pyran and chroman derivatives, coumarins and xanthone-type compounds was described in a review of recent progress on the chemistry of dimethyl acetylenedicarboxylate (14S537). The synthesis of several polysubstituted spirooxidole-2-amino-4H-pyrans, mainly through three-component reactions, was also described in a review on the synthesis of biologically active spirooxindoles (14T9735). 

The use of A/ -heterocychc carbenes (NHC) as catalysts in the preparation of3,4-dihydro-2H-pyran-2-ones (14EJ05631),the copper-catalyzed synthesis of 3-substimted isocoumarins from o-halobenzoic acids and 1,3-diketones (14JOC8507) and the synthesis and reactivity of pyridine-flised 3-substituted 2-amino-4-arylchromenes (14H(89)1557) have been reviewed. 

The biosynthesis of ochratoxin A has been studied using both and C-labeled precursors. In preliminary studies, Ferreira and Pitout (1969) showed that DL-[l- C]-jS-phenylalanine was incorporated into ochratoxin A by cultures of A. ochraceus. Hydrolysis of the labeled ochratoxin A with 6 N hydrochloric acid gave the isocoumarin acid 7 and L-jS-phenylalanine. The amino acid was found to contain all the activity. These results were confirmed by Steyn et al. (1970) and Maebayashi et al. (1972) using L-[f/- C]- -phenylalanine, as well as by Searcy et al. (1969) using [1- " C]-jS-phenylalanine. 

---