Mansonone

Figure 5. Structures of mansonones from Hibiscus tiliaceus...

The intramolecular Diels-Alder addition of a benzyne to a furan has been exploited in a synthesis of mansonone E (81TL4877). The benzyne (211), generated from the anthranilic acid (210), yields the adduct (212 86%) which is easily converted into the naphthalene (213 Scheme 79). A similar addition was achieved by generating the benzyne by treating an o -dibromobenzene with butyllithium. 

A facile peri-ring closure of dimethylnaphthol ether 1075 proceeds via ester hydrolysis and conversion to the corresponding acid halide followed by an intramolecular Friedel-Crafts acylation to afford the tricyclic chroman-3-one 1076, an intermediate during a formal synthesis of mansonone F (Equation 421) <2000CC1203>. 

Gerber has isolated (+ )-epicubenol (81) from a Streptomyces species. This compound is the enantiomer of that found in the essential oil of Cedrela toona Roxb. The syntheses of four naturally-occurring phenolic sesquiterpenoids obtained from the essential oil of elm wood have been reported, viz. (82 R = Me), (82 R = CHO), (83 R = Me), and (83 R = CHO). The known o-quinone, mansonone C (84), has also been isolated from elm wood. The structure (85) of sesquichamaenol, a minor component of the essential oil of Chamaecyparis forrnosensis, has been deduced on the basis of spectroscopic evidence and synthesis. Piers et al. have published complete details of their syntheses of a- and ) -cubebenes (86). 

A most detailed study by Japanese scientists of the mulberry tree has indicated a considerable range of benzfurans and other phe-nolics being formed in cortex and phloem tissues (27). Also, quino-noid phytoalexins, the mansonones, have been detected in infected elm trees (28). Furthermore, four methoxysubstltuted dibenzofurans... 

The precursor of the hexasubstituted benzene in jatropholone A and B was a Diels-Alder adduct formed when furan 190 and enone 191 were reacted under high pressure. Subsequent aromatization was initiated by treatment with dilute hydrochloric acid,Eq. 120 [177]. This strategy was also used to install the aromatic ring in the syntheses of mansonone E [178]. 

Synthesis. - Cycloadditions. A bis-heteroannelation approach to ( )-ligularone (90) from (89) has been reported. Other intramolecular cycloadditions include the conversions of (91) into (92) and the intramolecular addition to the benzyne (93), which is the key to the synthesis of ( )-mansonone (94). ... 

Best and Wege59have reported the first total synthesis of Mansonone F and this is described in Scheme 10. Phenol (111)60 was made to react with 2-chloroacetyl-5-methylfuran (112) in dimethylsulfoxide and sodium methoxide to yield (113). Ketalization of (113) followed by catalytic reduction and basic hydrolysis afforded anthranilic acid (114). Diazotization followed by pyrolysis with propene oxide in 1,2-dichloroethane probably yielded aryne (115), which undergoes intramolecular Diels-Alder reaction producing the adduct (116). Deoxygenation and then acid hydrolysis afforded the product (117). This was subjected to Grignard reaction. The resulting tertiary alcohol on nitration yielded the nitro compound (118) which was subjected to reduction and oxidation respectively to obtain (119). It yielded Mansonone F (120) on dehydration. 

Scheme 10 Phenol (111) was converted to compound (113), whose transformation to anthranilic acid (114) was achieved by standard organic reactions. Its conversion to adduct (117) was accomplished by subjection to four successive reactions (a) diazotization, (b) pyrolysis, (c) deoxygenation, (d) acid hydrolysis. This yielded nitro compound (118) by Grignard reaction, followed by nitration. Reduction of (118) and then oxidation of the resulting compound produced compound (119), which on dehydration afforded Mansonone F (120)...

Naphthoquinone (122)62 63 64 on reductive acetylation afforded diacetate (123). Selective basic hydrolysis afforded monoacetate (124). This on benzylation followed by basic hydrolysis and alkylation with chloroacetone yielded compound (125). Its cyclization was attempted with tetrafluroboric acid in ether. The resulting compound (126) was immediately oxidized with selenium dioxide to Mansonone F (120). 

Suh et al.65 have reported a formal total synthesis of Mansonone F and this is described in Scheme 12. 5-Methoxy-a-tetralone (127) was converted to 1-methyl-5-hydroxy-naphthalene (128) by the standard organic reactions. Treatment of (128) with phenyl boronic acid, paraformaldehyde and propionic acid followed by catalytic hydrogenation yielded compound (129). This on alkylation gave the compound (130) which on alkaline hydrolysis was converted to acid. The acid halide underwent intramolecular Friedal-Crafts acylation affording an intermediate (131) whose transformation to Mansonone F has been accomplished by Best and Wege.59... 

Baneijee et al.66 have developed an alternative synthesis of the compound (129) whose utility in synthesis of Mansonone F (120) has been reported by Suh and collaborators.65 This is described in Scheme 13. Tetralone (127) was reduced with sodium borohydride to alcohol which on alkylation with benzyl chloride produced benzyl derivative (132). Its conversion to (133) was attempted by treatment with boron tribromide in dichloromethane. C ompound (133) (characterized b y m ass s pectroscopy) was obtained in poor yield. The major product was the diol (134), whose structure was confirmed by spectral data. It indicates that the demethylation was accompanied by debenzylation. Treatment of diol (134) with triethyl orthoformate and aluminium chloride afforded aldehyde (135) which was subjected to catalytic hydrogenation to produce compound (136). It was transformed to ketone (137) by oxidation and then made to react with methylmagnesium bromide in ether. The resulting tertiary alcohol on heating with p-toluenesulfonic acid in toluene for 24 hr produced the naphthalene (129) in 78% yield. 

Dumas et al.67 isolated Mansonone A (138), Mansonone C (139), Mansonone D (140), Mansonone E (121), Mansonone F (120) and Mansonone G (141) from the elm ulmus americana infected with... 

Scheme 11 Naphthaquinone (122) was converted to compound (124) by the standard organic reactions. This on benzylation followed by alkylation and cyclization afforded compound (126), which on oxidation with selenium dioxide afforded mansonone F (120)...

Ceratocystis ulmi. These sesquiterpenes quinones possess antifungal properties. None of the mansonones was detected by TLC in extracts from healthy U. Americana. Accumulation of mansonones A, C, D and G in... 

One of the early examples of an intramolecular Diels-Alder reaction of benzynes involved cycloaddition to a furan that was tethered to the benzyne moiety . Diazoti-zation of anthranilic acid 669 gave in 86% yield the cycloadduct 670, which was subsequently converted to the o-naphthoquinone 671 (mansonone E 7 steps) as well as to the structurally related mansonones F and I and biflorin. ... 

Benzenoid (-)-(75, 105)-calamenene is isolated from Ulmus thomasii (Uhnaceae), and (-l-)-3,8-calamenenediol from Heterotheca subaxillaris. The naphthalene sesquiterpene cadalene oeeurs in eonifers, for example in flie resin of fir Abies sibirica (Pinaceae). The wood of several trees contains 3-cadalenol. Cadalen-2,3-qutnone, also known as mansonone C, is a constituent of Mansonia altissima and Ulmus lactinata (Table 3). 

The responsible allergens belong to the class of sesquiterpenoid mansonones, of which mansonone A, a red ortho-quinone is the main (strong) sensitiser (Schulz et al. 1979). Interestingly, some of these quinones, e.g. mansonone E and F, occur in the elm species Ulmus hollandica)y making the tree resistant to the Dutch elm disease. 

Milowood is a small tropical tree distributed widely throughout the tropics and in many areas of the United States, including California, Florida and Hawaii. Primarily, it is used for making bowls, bracelets, carved tikis and furniture. Among the different mansonones that are known sensitisers from Mansononia altissimUy Milowood contains a new sesquiterpenoidal quinone, named mansonone X (Milbrodt et al. 1997). 

Persistent occupational contact dermatitis has been observed in a Hawaiian bowl turner who was shown to be allergic to the mentioned constituent, mansonone X. This compound showed a moderate sensitising capacity in experiments with guinea pigs (Hausen et al. 1997). 

Mansonia altissima Mansonia, African black walnut Mansonone A may cross-react with Dalbergia spp. 10% Sawdust in pet. West Africa. Used as walnut substitute, also a mucosal irritant... 

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