Furanone compounds

Kim et al. describe the synthesis of biologically active furanone compounds (Table 1) involving the formation of an amino and a hydroxyl compound... 

Scheme 21 shows the synthesis of a dihydrofuran derivative 86. Synthesis of this compound was described by Nam et al. [68] utilizing a furanone compound 87 synthesized by Kim et al. [61] via a similar synthetic approach as described in Scheme 17. The lactone was reduced using lithium aluminum hydride to give the diol 88 and intramolecular etherification using the Mitsunobu reaction afforded the dihydrofuran 86 in moderate yield (47%).

The D. pulchra furanone compounds generally consist of a furan ring structure with a substituted alkyl chain at the C-3 position and a bromine substitution at the C-4 position (Fig. 5). The substituent at the C-5 position may vary in terms of side chain structure. The natural furanones are halogenated at various positions by bromine, iodine, or chlorine [128]. D. pulchra produces at least 30 different halogenated furanones which are stored in specialized vesicles and are released at the surface of the thallus at concentrations ranging from 1 to 100 ng/cm2 [132]. Field experiments have demonstrated that the surface concentration of furanones is inversely correlated with the degree of colonization by marine bacteria [133]. 

The natural furanone compounds exhibited little or no effect on the QS systems of P. aeruginosa and so have been chemically modified and screened for... 

Hentzer M, Riedel K, Rasmussen TB, Heydom A, Andersen JB, Parsek MR, Rice SA, Eberl L, MoUn S, Hoiby N, et al. Inhibition of quorum sensing in Pseudomonas aeruginosa biotilm bacteria by a halogenated furanone compound. Microbiology 2002 148 87-102. 

The direct combination of selenium and acetylene provides the most convenient source of selenophene (76JHC1319). Lesser amounts of many other compounds are formed concurrently and include 2- and 3-alkylselenophenes, benzo[6]selenophene and isomeric selenoloselenophenes (76CS(10)159). The commercial availability of thiophene makes comparable reactions of little interest for the obtention of the parent heterocycle in the laboratory. However, the reaction of substituted acetylenes with morpholinyl disulfide is of some synthetic value. The process, which appears to entail the initial formation of thionitroxyl radicals, converts phenylacetylene into a 3 1 mixture of 2,4- and 2,5-diphenylthiophene, methyl propiolate into dimethyl thiophene-2,5-dicarboxylate, and ethyl phenylpropiolate into diethyl 3,4-diphenylthiophene-2,5-dicarboxylate (Scheme 83a) (77TL3413). Dimethyl thiophene-2,4-dicarboxylate is obtained from methyl propiolate by treatment with dimethyl sulfoxide and thionyl chloride (Scheme 83b) (66CB1558). The rhodium carbonyl catalyzed carbonylation of alkynes in alcohols provides 5-alkoxy-2(5//)-furanones (Scheme 83c) (81CL993). The inclusion of ethylene provides 5-ethyl-2(5//)-furanones instead (82NKK242). The nickel acetate catalyzed addition of r-butyl isocyanide to alkynes provides access to 2-aminopyrroles (Scheme 83d) (70S593). 

Of these, the 2(5//)-furanones 2 are perhaps the compounds having the most interesting synthetic and biological importance. The synthesis and properties of compounds 2 have recently attracted much attention. The 2(5//)-furanone fragment is present in a wide variety of biologically active natural products (84MI1) moreover these furanones possess utility as valuable synthetic intermediates (86T3715). 

In the present review we emphasize (1) the recent developments in the synthesis of 2(5/7 )-furanones, covering the last six years (1995-2000), and (2) reactions of these compounds, as reported in the period from 1980-2000. 

Owing to their frequent occurrence in natural products and their synthetic utility, 2(5//)-furanones are important synthetic targets and intermediates. In considering the methods for the preparation of these compounds, we will emphasize the recent developments in this area. 

The 4-aryl-2(5// )-furanone unit proved to be present in many naturally occurring (91JOC6275) and medicinally important compounds (93JHC1581). Examples are the potent antibiotics rubrolide A-F 90a-f, isolated by Miao and Andersen from the colonial tunicate Ritterela rubra (Scheme 26) (91JOC6275). 

The different furanones 104 were tested for their potency as inhibitors of PGE2 production both in transfected Chinese hamster ovarian (CHO) cells expressing human COX-2 and in human whole blood. Compound 104r proved to be an orally active and selective COX-2 inhibitor that is devoid of the ulcerogenic effect at >100 times the dose for antiinflammatory, analgesic, and antipyretic effects (99BMC3187). 

Figure 10.1 Analysis of racemic 2,5-dimethyl-4-hydroxy-3[2H]-furanone (1) obtained from a strawbeny tea, flavoured with the synthetic racemate of 1 (natural component), using an MDGC procedure (a) dichloromethane extract of the flavoured strawbeny tea, analysed on a Carbowax 20M pre-column (60 m, 0.32 mm i.d., 0.25 p.m film thickness earner gas H2, 1.95 bar 170 °C isothermal) (b) chirospecific analysis of (1) from the sti awbeny tea exti act, ti ansfened foi stereoanalysis by using a pemiethylated /3-cyclodextrin column (47 m X 0.23 mm i.d. canier gas H2, 1.70 bar 110 °C isothemial). Reprinted from Journal of High Resolution Chromatography, 13, A. Mosandl et al., Stereoisomeric flavor compounds. XLIV enantioselective analysis of some important flavor molecules , pp. 660-662, 1990, with permission from Wiley-VCH.

Sotolon (4,5-dimethyl-3-hydroxy-2(5H)-furanone) and solerone (4-acetyl- y-butirrolactone) were claimed to be responsible for some aroma characteristic of flor sherries wines. These compounds are present only as traces, and are chemically unstable. A system of two gas chromatographs coupled with a four-port switching valve was used to quantitate these components without previous fractionation. The first chromatograph was equipped with an on-column injector, in order to avoid thermal degradation of sotolon in the heated injector, a DB-5 column and an FID. The second chromatograph was equipped with an on-column injector, a DB-1701 column and an FID. The method allowed quantification of solerone and sotolon at concentrations as low as a few ppb (29). 

Another route to the synthesis of the furanone-containing compounds (e.g., 84, Scheme 18) is via magnesium-mediated carbometallation of propar-gyl alcohols, as described by Forgione et al. [67]. Scheme 20 demonstrates this procedure as a feasible means of producing the Merck anti-inflammatory drug Vioxx, 85. 

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