Nemorensic acid

The structure and absolute configuration of m-nemorensic acid (75) obtained by alkaline hydrolysis of retroisosenine (Table30iv) and doro-nenine (Table 3 O iv), has been determined by Kirfel et al 159), using X-ray crystallography. 

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Stereoselective reduction of chiral 2-furoic amides has been studied in detail and used as a key step in the synthesis of (+)-nemorensic acid <00JCS(P1)3724> <00CC465>. 

Over the past several years, Mascarenas and co-workers (150-153) utilized the oxidopyrylium ion with variously hetero-substituted olefin tethers. Mascarenas has used this methodology in tandem with a Diels-Alder reaction to prepare tricyclic cycloheptanoid substrates. Further, Mascarenas and co-workers (154—156) achieved the synthesis of optically active oxabicyclic[3.2.1]octane derivatives through the addition of a homochiral p-tolylsulfinyl group substituted at the olefin tether. The Mascarenas group has also used this methodology to prepare the THF portion of ( )-nemorensic acid via oxidative cleavage of the substituted a-hydroxyketone moiety (157) (Scheme 4.78). 

Bulgarsenine (61) has also been isolated from Senecio doronicum L. together with a new alkaloid, doronenine (62).28 The structure and absolute configuration of doronenine were established by X-ray structure analysis.29 The structure (63) of the saturated y-lactone (ds-nemorensic acid) that was obtained on alkaline hydrolysis of doronenine was also determined by X-ray crystallography.30... 

The alkaloid nemorensine (C18H2705N mp 132-134° [a] 4 —58°) was shown to have structure 160a on the basis of spectral and chemical evidence. The basic moiety resulting from the alkaline hydrolysis could not be crystallized either as such or as its picrate. The acidic fragment was named nemorensic acid (mp 174-178° [a]f,4 +87°). The same alkaloid was isolated from a number of subspecies (155a). 

The synthesis of senecivernic acid (29)14 and nemorensic acid in the open-chain form (30)15 has been claimed. These acids were presumably formed as part of mixtures of diastereoisomeric racemates, since no steric control was exercised in either route, nor were any of the mixtures separated. No comparisons were made with natural material. 

Bicyclic ether 124, obtained from the intramolecular cycloaddition of 123, was subjected to ozonolysis with a reductive work-up, Eq. 90. Silyl protection gave alcohol 125 and reduction transformed the thioether linkage into the vicinal cis dimethyl groups found in ( )-nemorensic acid [137]. 

The reaction of diazo compounds 717 with a C=0 or C=N bond produces the carbonyl or azomethine ylides 718, which undergo subsequent hetero-[3 + 2]-cycloaddition reaction, giving the five-membered heterocyclic compounds 719 (Scheme 2 2 3).297298 Hodgson et al. reported a concise, stereoselective synthesis of cis-nemorensic acid via the tandem carbonyl ylide formation-cycloaddition.2971 The reaction of the di-azodione 720 with propargyl bromide in the presence... 

Heterocyclic aromatic compounds can sometimes be reduced, particularly those which are electron-deficient. For example, reduction of pyridines gives 1,4-dihydropyridines (which are readily hydrolysed to 1,5-dicarbonyl compounds). Partial reduction of five-membered heteroaromatic compounds such as furans and pyrroles is also possible if these have electron-withdrawing substituents to stabilize the intermediate radical anion. For example, reduction of the furan 71 occurred with high selectivity to give the dihydrofuran 72, used in a synthesis of (-l-)-nemorensic acid (7.51).24... 

Moeller synthesized tetrahydrofuran natural products (+)-linalool oxide <01OL2685> and (+)-nemorensic acid <01TL7163> by employing intramolecular coupling reactions of enol ether radical cations as well as ketene dithioacetal radical cations with oxygen nucleophiles. 

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