Sesquiterpenes, macrocyclic

Other applications of this method include, e.g. the synthesis of the antibiotic A26771B (5i) [118] and the marine cembranolide isolobophytolide [119], Trost and Warner [120] reported that a-sulfonyl sulfones can also serve as the substrates of ir-allylpalladium complexes for macrocyclization. Furthermore, an a-hydroxy-carbonyl ketone was alkylated intramolecularly by a a-allylpalladium complex in the total synthesis of the macrocyclic sesquiterpene humulene [121]. 

An intramolecular alkylation of a-thionitrile (58) leads to a macrocycle, an intermediate for the synthesis of the sesquiterpene (-)-dihydrogermacrene D (Scheme 29). Alkylation of an a-cyanosulfone followed by reduction gave a-substituted acetonitriles. Cyclization of a 1,3-dibromoalkane with (methylthio)acetonitrile yields a l-cyano-l-(methylthio)cyclobutane, a precursor for the synthesis of cyclopentanones. Reaction of a-(arylthio)nitriles with aryl halides in the presence of LDA and BusP at -78 C affords cyanostilbenes. ... 

Trichothecenes from Pusarium, Stachybotrys, and Trichoderma, among others. Note Trichothecenes include sesquiterpenes with a trichothecane skeleton, olefinic groups at C-9 and C-10, and epoxies at C-12 and C-13. Macrocyclic trichothecenes have a carbon chain between C-4 and C-15 in an ester or ether linkage (e.g., T-2 toxin, DON, satratoxins G and H verrucarins B and J, trichoverrins A and B)). 

From a structural standpoint, these compounds consist of a trichothecane sesquiterpene diol linked through ester bonds to a diacid derived from esterification of the ( )-acid of a (Z, )-muconic acid with a 5-hydroxypentanoic acid segment (containing various substitution patterns). As the synthesis of the sesquiterpene diol unit is beyond the scope of this chapter, we have limited discussion to the methods employed for formation of the macrocyclic ring of these substances. Papers concerning the construction of the various trichothecane diol systems may be found by consulting the references cited in this section. 

Members of the Celastraceae family produce a wide variety of macrocyclic sesquiterpene pyridine alkaloids, which will be discussed below. In addition, various nicotinoyl esters of the base sesquiterpene structure p-dihydroagarofuran are produced, such as in the cangorins [160], wilforcidine [161], triptofordinines [162], and related compounds [163]. 

Khat, a drug produced from leaves and shoots of Catha edulis, is used as a stimulant, primarily in East Africa and Southern Arabia [167]. Interest in this drug led to investigation of the components of C. edulis, which included a number of macrocyclic sesquiterpene pyridine alkaloids, the cathedulins. 

Celastraceae also elaborate other, more complex, alkaloids, also polyester sesquiterpenes, incorporating a macrocycle derived from an evonic, wilfordic, cassinic or other type pyridine dicarboxylic acid with an additional alkyl chain of the basic eudesmane cycle at C-3 and C-7 (Table III). Celastraceae alkaloids are well-documented for the European and Asian genera, particularly Catha, Celastrus, Euonymus and Trypterigium but are relatively rare among the Latin... 

An alternate route to the serrulatanes involves formation of a macrocyclic intermediate (a germacrene isoprenologue) analogous to that implicated in the biosynthesis of the cadinane sesquiterpenes (91). 

Fig. (12). Basic sesquiterpene cores of the macrocyclic sesquiterpenes alkaloids...

Fig. (13). Macrocyclic sesquiterpene alkaloids from Catha edulis...

Fig. (20). Active macrocyclic sesquiterpenes from Moytenus krukovii...

A total of 217 trichothecenes, based on the sesquiterpene skeleton (1) named trichothecane (4), which replaced the earlier (5) scirpane nomen-clature have now been reported from natural sources. They are made up of 133 (61%) non-macrocyclic and 84 (39%) macrocyclic compounds. Thus, 20 new non-macrocyclic trichothecenes have been isolated since 1995 and 17 new macrocycles since 1991. 

In the first category soldiers of some genera of the primitive mandi-bulate nasutes produce normal alkanes, simple mono- and sesquiterpenes and a homologous series of macrocyclic lactones with 22 to 36 carbon atoms (531). 

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