Of guaianolides

The subsequent transformation of these cycloadducts further illustrates the versatility of this approach in the construction of guaianolide sesquiterpenes (Scheme 1)7 The moiety incorporated in the adduct allows for the introduction of diverse functionalities at C-S and C-2. For example, reduction of the cycloadduct (11) with sodium borohydride produces a good yield of the iron complex (16). Oxidation of this complex with cerium ammonium nitrate gives methyl ester (17). In addition, (11) reacts with nucleophiles such as lithium dimethylmalonate and methanol to give the alkylated complex (18) and the meth-oxylated complex (19), respectively. Oxidative demetallation of (11) with bromine leads to selective replacement of the moiety at C-2 by bromide. ... 

In addition to the sulfoximines, Johnson has studied phosphinothioic amides as alkene precursors. This reagent has not achieved the popularity of the sulfoximines. It can be utilized for ketone methylen-ation with resolution, as well as for Ae synthesis of more highly substituted alkenes. Rigby has found that in the synthesis of guaianolides this reagent was effective where Peterson and Wittig reactions gave only p-elimination. ... 

Eremanthus elaeagnus has led to an investigation of its use as a synthetic precursor of guaianolides which have potential as antitumour agents. Kessanol (579) and 8-epikessanol (578) have been synthesized for the first time by a reaction sequence in which the hydroazulene system is constructed by an ene reaction of the aldehyde (575) (c/. Scheme 57) and the cyclic ether functionality is... 

A review has recently appeared describing the synthesis of hydroazulene sesquiterpenes through rearrangement of substituted hydronaphthalene precursors, including some syntheses of guaianolides from santonin (1)... 

This transformation is the first step in several recent syntheses of guaianolides and related compounds. 

The overall yield of this synthesis was poor and so the same authors devised a new sequence starting from compound 206, obtained from santonin in 10 steps in 23% overall yield (Scheme 27). Solvolysis of 206 gave, in 75% yield, a 2 1 3 mixture of guaianolides 207, 208 and 209, which possess tetra-, tri-, and di-substituted double bonds, respectively. It is likely that the solvolytic rearrangement of206 proceeded via 210, since... 

Stereoselective rearrangement of guaianolides bearing a double bond at the C(6)/C(6a) position occurs to give tricyclic S-valerolactones (Scheme 44). ... 

Thapsigargins A Well-Studied Group of Guaianolides from Apiaceae. 3090... 

Biological properties and chemotaxonomic value of guaianolides have encouraged intensive studies. The best studied example is thapsigargin from Thapsia garganica L. 

Different procedures for the synthesis of guaianolides have been reviewed [16]. Some of these will be discussed in the following paragraph. 

A number of stereoselective syntheses of guaianolides have been based on the masked 3-hydroxycyclopentanecarboxylic acid (64) prepared from (S)-carvone (59) as illustrated in Scheme 98.8 [20]. 

Scheme 98.7 Synthesis of the starting material 46 for preparation of guaianolides...

Scheme 98.11 Formations of guaianolides and eudesmanolide in Asteraceae through 1,10 and 4,5 epoxidation of costunolide (82) [51]...

Notice that the suggested intermediate carbocations are tertiary carbocations but that the epoxides during the formations of guaianolides are attacked at the less substituted carbon atoms. 

Scheme 98.12 Proposed biosynthesis of guaianolides in Apiaceae, here depicted to afford thapsigargin (11) [5], A 1,10-epoxide is suggested as an intermediate...

This chapter gives an overview of the chemistiy, biochemistry, and pharmacology of guaianolides, mainly from the two plant families Asteraceae and Apiaceae. At present, the guaianolide most likely to become drugs are derivatives of thapsigargin. 

Various guaianolides occur in higher plants, particularly in Compositae. This is the first isolation of guaianolides from the lower terrestrial plants. 

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