Of elemanolides

The synthesis of elemanolides from santonin requires cleavage of the C(2)-C(3) double bond. In a synthesis of saussurea lactone by Ando (Scheme 30) [41], cleavage of this bond was carried out by treatment of epoxymesylate 206 with aluminum isopropoxide, which afforded... 

Complete details of the previously reported total synthesis of the antitumour elemanolides vernolepin (363) and vernomenin (364) (Vol. 7, p. 97) have been published.Other research groups have reported the synthesis of compounds (365)—(367) which could be of considerable value as intermediates in alternative synthetic routes to vernolepin and vernomenin.The antitumour activity of... 

A few individual terpenoids, as well as less expensive mixtures of these compounds, find practical applications. Some examples are the tli terpenoid Vitamin A, the sesquiterpenoid santonin (as an anthelmintic), and the pyrcthnns, pyrctholonc esters of the monoterpenoid chrysanthcmic acid (used as an insecticide). A number of sesquiterpenoid lactones of the germacranolide. guaianolide and elemanolide types have shown promise as rumor inhibitors. 

The antitumour activity of the elemanolides vernolepin (393) and vernomenin (394) has stimulated several research groups to solve the problems associated with... 

Reduction of the photo-adduct (446) derived from (+)-isopiperitone and cyclobutene-1-carboxylic acid with NaCNBH3 gives the lactone (447). Thermolysis of this compound affords the 6a-epimer of isoaristolactone (448) and the elemanolide (449).213 A novel approach to the synthesis of germacranes involves the thermal opening of a bridgehead cyclobutene which, in turn, is derived by an oxy-Cope rearrangement (Scheme 57).214... 

The structure and stereochemistry of the C,4a.H5/J elemanolide 31 (elemanschkuhriolide, from Schkuhria schkuhrioides) is deduced from a Cope rearrangement of schkuhriolide 30 (isolated from the same plant source, Iva frutescens), a melampolide with a lactone ring closed at C-8 and cis annulated1043. 

The significant antitumour and cytotoxic properties of vernolepin (436) and, to a lesser extent, vernomenin (437) have stimulated general interest in the natural occurrence and total synthesis of 2,3-secoeudesmanolides or elemanolides cf. Vol. 8, p. 111). Two new alternative multi-step syntheses of vernolepin (436) have recently been accomplished by independent research groups using the reaction sequences outlined in Schemes 41 and 42. 

A total synthesis of ( )-temisin (439) from the known acetal-ketone (438) (Scheme 43) and n.m.r. analysis at 250 MHz have confirmed the structure and established the stereochemistry of this compound.An interesting new approach to the 2,3-secoeudesmanolide (elemanolide) framework has been sucessfully applied to the synthesis of saussurea lactone (442) cf. Vol. 8, p. 97). 

A further example of the co-occurrence of germacranolides, eudesmanolides, 2,3-secoeudesmanolides (elemanolides), and guaianolides is provided in a recent paper which describes the isolation of compound (453), callitrisin (454), 1,2-dihydrocallitrisin, callitrin (455), columerallin (456) and 11,13-dihydrocolu-... 

Synthesis of 6,12-sesquiterpenolides This section describes the synthesis of sesquiterpenes bearing a lactone moiety between C(6) and C(12). The transformation of the A-ring in santonin to give eudesmanolides, guaianolides, and elemanolides, as well as the modification of the lactone ring is described. Some microbiological transformations of santonin and its derivatives are also described. 

Ozonolysis of the C(2)-C(3) double bond has been used by two Japanese groups in two different synthetic approaches to 8-deoxyvemolepin (259), a functionalized elemanolide that shows potent activity against tumor cell cultures in vitro. 

Around 60 elemanes are known at present and some of these have been isolated from woody tissues. (-)-Elemol (206) was first isolated in 1907 (350) from Manila elemi oil obtained from the oleoresin of Canarium luzonicum. (-)-)ff-Elemene (209) (238, 396), shyobunone (210) (419), and a few related elemanes occur in the essential oil from rhizomes of Acorus calamus, Resin from Ferula spp. (Galbanum resin) contains 10-epi-elemol (211) (391). The furane derivative, curzerenone (212), has been isolated from rhizomes of Curcuma zedoaria (195). The majority of presently known elemanes have a lactone ring and are known as elemanolides they have been recently rewiewed (146). Callitrin (213) is an example of an elemanolide that has been isolated from the heartwood of Callitris col-umellaris (59). 

Two elemanolide sesquiterpenes, vernolepin (XLVIIa) arid vernomenin (XLVIII) isolated from Vernonia hymenokpis are active against W 256 at 12 and 40 mg/kg respectively. Their structures were deduced by x-ray analysis of vernolepin /vbromobenzenesulphonate, (XLVIIb) and chemical... 

SCHEME 13.4. An asymmetric Heck reaction in the total synthesis of the elemanolide sesquiterpene dilactone (- -)-vernoIepin 9. 

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