Heterocyclics isocoumarins

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... 

Isocoumarins, such as bergenin (1.23) have a structure similar to coumarins, but the position of the oxygen and carbonyl groups within the oxygen heterocycle are reversed. Isocoumarins also play a role in defense responses. For example, bergenin has been shown to inhibit the growth of the powdery mildew on pea (Prithiviraj et al., 1997). 

Tanahashi T, Takenaka Y, Nagakura N, Hamada N, Miyawaki H (2000) Two Isocoumarins from the Cultured Lichen Mycobiont of Graphis sp. Heterocycles 53 723... 

The intramolecular reaction of alkenes with various O and N functional groups offers useful synthetic routes to heterocycles [69-71]. The isocoumarin 83 is prepared by the intramolecular reaction of 2-(2-propenyl)benzoic acid (81) with one equivalent ofPdCl2(MeCN)2. However, the (Z)-phthalide 82 is obtained from the same acid with a catalytic amount of Pd(OAc)2 under 1 atm of 02 in DMSO. 02 alone is remarkably efficient in reoxidizing Pd(0) in DMSO. The isocoumarin 83 is obtained by the reaction of 2-(l-propenyl)benzoic acid (84) under the same conditions [2]. 2-Vinylbenzoic acid was converted to the isocoumarin, but not to the five-membered lactone [72,73]. 

Some typical examples [39] include the carbonylation of 2-halophenols or 2-ha-loanilines to 0- or iV-heterocycles, and intramolecular enolate or enamine trapping to isocoumarins or quinolinones. In this respect, the carbonylative cyclization to indanones and tetralones with different late transition-metal complexes (Pd, Co, Ni) has been studied (eq. (12)) [40]. 

Pyridopyrimidines and pyrimidines fused with five- or six-membered heterocycles can be prepared via the ring closure of intermediate ethynylpyrimidines, which are themselves obtained by the Pd-catalyzed cross-coupling of halopyrimidines with alkynic compounds (Scheme 34). ° ""° o-Alkynylanilines such as (51), which are made by Pd-catalyzed coupling reactions of alkynes with o-haloaniline precursors, are easily cyclized to the indoles in the presence of base (Scheme 35). " " Similar meth( s can be employed in the synthesis of isocoumarins," thienopyridines," furopy-ridines" and the marine alkaloid asptamine." ... 

Hydroxypyridine (201) itself possesses latent 1,3-dipolar character because of tautomerism involving 1-protiopyridinium 3-oxide (202). Aprotic diazotization of anthranilic acid in the presence of 201 gives two heterocyclic products [196 (20%) and 203 (23%)] which were isolated in separate experiments run under almost identical conditions.103,105 Formation of the bis-adduct 196 must involve cycloaddition of benzyne to 202 and N-phenylation and there is some evidence from related additions to 2//-phthalazin-1 -one (208) that the steps occur in this order.3 7b Formation of the isocoumarin structure 203 apparently involves electrophilic substitution of 201 by the benzyne precursor 5, followed by lactonization. From 3-hydroxy-6-methylpyridine compounds analogous to 196 and 203 were also obtained (10 and 29%, respectively). 3-Hydroxyquinoline afforded only the corresponding isocoumarin 204 (20%) whereas 4-hydroxyisoquinoline gave 4-phenoxyisoquinoline (12%) and the bis-adduct 205 (12%) with benzyne.103,105... 

The formation of oxetanes by photochemical (2 + 2)-cycloaddition of carbonyl compounds, such as aldehydes, ketones, and quinones, with carbon-carbon double bonds has been reported for various heterocyclic compounds. Maleic anhydride,142 isocoumarin (and its derivatives),143,144 benzol 61 thiophene 1,1-dioxide,144 l,3-dihydroimidazol-2-ones,131,132... 

The intramolecular reaction of alkenes with various O and N functional groups offers useful synthetic methods for heterocycles [15,16,40]. Reaction of unsaturated carboxylic acids affords lactones by either exo or endo cyclization depending on the positions of the double bond. Both 5-hexenoic acid (83) and 4-hexenoic acid (84) were converted to five- or six-membered lactones depending on the solvents and bases [41,42]. Oxidative cyclization of the optically active 4-pentenoic acid derivative 85 (85 % ee) using O2 as an oxidant afforded the y-lactone 86 with 86 % ee in 84 % yield [43]. 2-Vinylbenzoic acid (87) was converted to isocoumarin (88), but not to the five-membered lactone [41,44]. 

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 generation of more or less exotic thioamides by cleavage reactions of sulphur heterocycles such as 1-thio- and 1,2-dithio-isocoumarins, ... 

Isocoumarins are an important class of heterocyclic scaffolds that exhibit a wide range of biological activities, such as antifungal, antibacterial, and antidiabetic effects. In 2012, several copper-catalyzed procedures for the synthesis of isocoumarins were developed. Xi and co-workers developed an... 

---