3.4- Dihydroisocoumarin ring

We present here a review of our studies on the isolation, structure elucidation and biological activities of xenocoumacin 1 (1) and 2 (2). As well, we review the work of others on related compounds that contain the 3,4-dihydroisocoumarin ring system. In particular, the AI-77 and amicoumacin compounds, whose chemical structures and pharmacological activity are very similar to the xenocoumacins, will be discussed with respect to their structure... 

The xenocoumacins exhibit UV spectra in neutral and al)solutions similar to that of mellein (ref.12) and characteristic of the 8-hydroxy-3,4-dihydroisocoumarin chromophore. The Xmax (MeOH) occurs at 247 and 314 nm. Upon addition of alkali there is a bathochromic shift from 314 to 347 nm. Similar UV spectra were also reported for the amicoumacins (ref.101), baciphelacin (ref.102) and all the AI-77 compounds except AI-77-G (ref. 99). With AI-77-G (33), the dihydroisocoumarin ring has been hydrolysed causing a shift in Xmax (MeOH) to 298 nm. The 8-hydroxy-3,4-dihydroisocoumarin ring system also exhibits a characteristic fluorescence spectrum. 

The total synthesis of the natural furano-fused dihydroisocoumarin (+)-monocerin was accomplished in 15 steps with a 15.5% overall yield starting from but-3-en-l-ol via tandem dihydroxylation-SN2 cyclization and a copper-catalyzed tandem cyanation-lactonization process (140BC5973). The formation of the 3,4-dihydroisocoumarin ring in the total synthesis of natural (+)- and unnatural (-)-scorzocreticin involves a palladium-catalyzed intramolecular carbonylation and lactonization of l-aryl-2-(2-iodoaryl) ethan-l-ol (14T8161). 

The isocoumarin and the dihydroisocoumarin ring systems occur widely in nature Their synthesis by lithiation method is according to type C and involves ortho metalation of N-methyl arylcarboxamides. The organometallic compounds on treatment with electrophilic reagents such as an epoxide or allylbromide followed by hydrolysis and cyclisation furnish the dihydroisocoumarins. Bromination at benzylic position followed by dehydrobromination then gives the isocoumarins themselves. 

Catalytic reduction of isocoumarins leads to 3,4-dihydroisocoumarins but LAH opens the pyranone ring to form phenethyl alcohols. 

Treatment of 3,4-dihydroisocoumarins with 2-methylthiophenoxide results in cleavage of the pyran ring and formation of 2-thioethylbenzoic acid derivatives. Sequential cyclization, bromination and dehydrobromination afford the isothiocoumarins via the 3,4-dihydroisothiocoumarin (Scheme 198) <2000T6763>. 

Dihydrocoumarins and Dihydroisocoumarins. - The potential of thalHum compounds in organic synthesis continues to be developed in a variety of reactions. One of these was the synthesis of dihydrocoumarins by oxidative cyclization of 3-arylpropionic acids, e.g. (177), by thallium(in) trifluoro-acetate-trifluoracetic acid (TTFA). The coumarin was accompanied by methyl 3-(2-hydroxyphenyl)propionate (178), which was formed by ring-... 

Hydroxy-l-methoxyallenyl-4,4-dialkylisochromans, available from dihydroiso-coumarins, undergo a Pd(0)-catalysed ring expansion to benzoxepanones. In the absence of the Pd catalyst, the dihydroisocoumarins can be converted direetly into a benzoxocanone (Scheme 20) <04SL481>. 

Another C—H activation strategy for lactone synthesis involves the ring closure of benzoic acids with dihaloalkanes [111]. Yu and coworkers recently developed a directed C—H functionalization/alkylation approach using Pd catalysts. Direct access to phthalides and 3,4-dihydroisocoumarins was possible using dibromo-methane and 1,2-dichloroethane, respectively (Scheme 2.56). 

Many ortho substituted-benzenesulfonylureas have recently been commercialized as herbicides. This discovery initiated a program to incorporate the ortho group of the benzenesulfonamide into a second ring, forming a bicyclic sulfonamide. The synthesis of a variety of bicyclic arylsulfonamides, such as, dihydrotenzothiophenes, benzothiopyrans, dihydroisocoumarins, dihydrobenzothiazine-dioxides, indanones and benzisothiazoles, is described. 

Hydroxyisocoumarins such as ustic acid (76) exist in equilibrium with the corresponding keto acids. For this review they are treated as isocoumarins. Isocoumarins with 3,4-, 4,5- and 7,8-fused carbocyclic rings are listed in Table 5. 3,4-Dihydroisocoumarins are often found together with the corresponding isocoumarins, particularly for the 7,8-fused carbocyclic isocoumarins. These are listed together in the Tables. 

Belgaonkar, V.H., and R.N. Usgaonkar Isocoumarins Part XIX. Synthesis of 8-Hydroy-3-methylisocoumarin and ( )-Mellein from w-Dinitrobenzene and a Convenient Synthesis of 3-Methoxyhomophthalic Acid. Indian J. Chem. 17B, 430 (1979). Bellinger, G.C.A., W.E. Campbell, R.G.F. Giles, and J.D. Tobias Formation of Some 3-Aryl-3,4-dihydroisocoumarins by Thermal Ring Closure of Stilbene-2-carboxylic Acids. J. Chem. Soc. Perkin Trans. 1 1982, 2819. 

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