Trichothecene ring

Tsang and Fraser-Reid effected an unusual ring-forming reaction during synthetic studies aimed at the carbon skeleton of the trichothecene group of terpenes (Scheme 16) [33]. 

Figure 28 Structures of Fusarium trichothecenes (including trichothecene intermediates isolated as natural products). The side chains (e.g., hydroxyl, acetyl, keto) are added to the trichothecene skeleton at C-3 (FT), C-4 (R2), C-15 (R3), C-7 (R4), and C-8 (R5), which are shaded in colors. While type A trichothecene has a single bond at C-8, type B trichothecene has a keto at C-8. Three rings that constitute the trichothecene skeleton [EPT R1 = (1), R2 = (1), R3 = (1), R4 = (1), R5 = (1)] are labeled A, B, and C in bold. It should be noted that EPT is not a Fusarium trichothecene.

The defined geometry of these steps has permitted the synthesis of some cycloheptane acids related to terpenoid natural products. The key reaction was the rearrangement of a suitably substituted bicy-clo[4.2.0]octane. Thus the photoaddition of ethylene to 3-methylcyclohexenone gave the ketone (42), which was converted to the alcohol (43). On treatment with HgO and HBF4 this gave the unstable hydroxy aldehyde (44), which was readily oxidized to the dicarboxylic acid (45 Scheme 17).- Ring expansion methodology was also used in an approach to the synthesis of the trichothecenes (see Scheme 18).32... 

It should be noted that while these compounds show potent in vivo antileukemic activity against P-388 leukemia in mice, very similar compounds, e g., roridin D, Fig. (61) show no in vivo activity. The key difference seems to be the presence of an oxygen substituent in the ring A of the trichothecene nucleus in the baccharinoids. More recently, screening of plants from South America for antineoplastic activity and subsequent assay-guided fractionation resulted in the isolation of several pentacyclic triterpenoids as active constituents from some Baccharis spp [85],... 

Some trichothecenes, a group of mycotoxins, have macrodiolide or macrotri-olide skeletons. Trichothecenes inhibited protein synthesis by binding to the ribosomal peptidyltransferase site [141]. Roritoxins (roritoxin A, 113) are 16-membered ring macrodiolides isolated from Myrothecium roridum [142]. Verru-carin A (114) is an 18-membered ring macrotriolide produced by Myrothecium spp. [143]. 

Many trichothecenes contain ester groups, whereas others contain alcoholic 0-H groups. The ester part of trichothecenes is hydrolyzed to alcohols when heated with dilute alkalies. Treatment with concentrated acid or rigorous boiling in water can open up the epoxy ring. 

Epoxytrichothec-9-en-8-ones (Table 2) are often referred to as Type B trichothecenes [Group III on the chemical classification (2), based on ring A chemistry] the remaining simple trichothecenes, without a keto group at C-8, are Type A (Groups I and II of the chemical classification). 

Brooks DE, (jrothaus PG, Palmer JT (1982) Synthetic Studies of Trichothecenes, an Enantioselective Synthesis of a C-Ring Precursor of Anguidine. Tetrahedron Lett 23 4187... 

There are more than 170 known trichothecenes which can be classified in four categories (A, B, C, and D) according to their chemical structure (Krska et al., 2001). All trichothecene mycotoxins have a basic tetracydic sesquiterpene structure with a six-membered oxygen containing ring, an epoxide group on the 12,13 position, and an olefinic bond on the 9,10... 

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