13-Lactaranolide sesquiterpenes

5-Lactaranolides constitute the largest group of sesquiterpenoids isolated from Lactarius species. Thus part 11 includes more than 90 compounds, of which ca. 30 were isolated from extracts of Lactarius, the 

Most natural 5-lactaranolides possess one double bond in position 6(7) (lactarorufins 11.28, 11.30, 11.34 etc.), with exceptions where the unsaturation is at position 4(6) (11.22, 11.26, 11.29) a few conjugated (11.7, 11.12, 11.16) and deconjugated (11.10, 11.11, 11.13, 11.17) dienes are also known. So far, only two examples of lactarane trienes have been reported (11.1, 11.3). 

Three examples of 8-keto-5-lactaranolides (11.1, 11.2, 11.4) as well as three examples of epoxy-derivatives (11.2, 11.14, 11.57) were isolated. 

Simple circular dichroic method for the determination of absolute configuration of 5-substituted 2(57/)-furanones has been established (772). Using this method absolute configurations of lactarorufin A 

Thanks to the presence of hydroxy groups, simple reactions such as esterifications, oxidations, dehydration were extensively performed for 

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The same authors assigned the structure 11.1 to a new polyunsaturated 5-lactaranolide sesquiterpene isolated from an ethanol extract of L. vellereus (56). 

With respect to the aliphatic moiety (cyclopentene ring, plus protons at C-3, C-4, and C-12), 8,9-secofuranolactaranes gave NMR spectra resembling those of 8,9-seco-5-lactaranolide sesquiterpenes (Part 14) in addition, the two protons on the furan ring exhibited the characteristic couple of signals at 57.20-7.36. Remarkably, when a carbonyl group is attached to C-7, as in compounds 19.1 and 19.3, the signal of H-13 is shifted downfield to 57.95. 

Scheme 18 is the Me2AlCl catalyzed ene cyclisation of 8,9-seco-furanolactarane and 8,9-seco-5-lactaranolide sesquiterpenes exemplified by compound 14.1 to the corresponding lactarane sesquiterpenes such as 11.10 98). Lactone (11.10) exhibited the unusual cis configuration between H-8 and H-9. The emergence of this stereorelationship could be anticipated by examining the Dreiding models of the two possible transition states 25.5 and 25.6 (Scheme 19). In fact, unfavourable steric interactions developing between the C-3 methyl group and the bulky >C=0 -Al- complex are minimized in the transition state 25.6, which eventually collapses to lactone 11.10 98).

The new lactone 16.6, one of the few known natural 13-lactaranolides, has recently been isolated from L. vellereus (87). The simulated C-NMR spectra of compound 16.6 suggested that the configuration at C-3 was opposite to that of isomeric lactaroscrobiculide A (16.2). This stereochemistry was established unequivocally by correlation of sesquiterpene 16.6 with 3-deoxy-3-epi-lactarorufin A (11.20), as shown in Scheme 10 (87). 

Structure elucidation of 5-lactaranolides other relevant chemical transformations involved the conversion of the lactone into the furan ring and addition reactions to double bonds (hydrogenation, hydroboration, epo-xidation, osmylation). A brief account of these reactions will be included in the chapter on chemical conversions of Lactarius sesquiterpenes. 

Lactaranolide derivatives included in Part 12 are produced by silica gel degradation of velutinal esters (7.28, 7.30), methylvelutinal (7.17) or free velutinal itself (for a discussion of these transformations see the chapter on chemical interconversions of Lactarius sesquiterpenes). The compounds upon acidification underwent aromatization to form furanoid derivatives (see Part 18). Under these conditions dehydration reactions took place and also dienes were formed (72). 

As expected, Pd catalysed hydrogenation of the C3-C4 double bond of lactone 16.15 (Scheme 7) afforded the dihydroderivative 16.17 in which the C-3 methyl group was trans to H-2 (94). Comparison of the NMR data of compound 16.5, readily prepared from 16.17, with those of natural lactone 16.6 (Scheme 6) definitely proved the stereostructure of the latter sesquiterpene (94). Compound 16.6 was also synthesized from 5-lactaranolide 11.28 according to the reaction sequence shown in Scheme 6, which is a nice example of a general strategy for moving the carbonyl group of lactaranolides from C-5 to C-13 (94). 

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