Tetracyclic sesquiterpenoid

Several species of Fusarium infect com, wheat, barley, and rice. Under favorable conditions they elaborate a number of different types of tetracyclic sesquiterpenoid mycotoxins that are composed of the epoxytrichothecene skeleton and an olefinic bond with different side chain substitutions (fig. 9). Based on the presence of a macrocyclic ester or ester-ether bridge between C-4 and C-15, trichothecenes are generally classified as macrocyclic (type C) or nonmacrocyclic (types A and B) (table 5). Other fungal genera producing trichothecenes are Myrothecium, Trichoderma, Trichothecium, Acremonium, Verticimonosporium and Stachybotrys. The term trichothecenes is derived from trichothecin, the first compound isolated in this group [115, 147-153]. 

The first enantioselective total synthesis of tetracyclic sesquiterpenoid (+)-cyclomyltaylan-5a-ol, isolated from a Taiwanese liverwort, was accomplished by H. Hagiwara and co-workers. They started out from Hajos-Parrish ketone analogue, (S)-(+)-4,7a-dimethyl-2,3,7,7a-tetrahydro-6/-/-indene-1,5-dione, that could be synthesized from 2-methylcyclopentane-1,3-dione and ethyl vinyl ketone in an acetic acid-catalyzed Michael addition followed by an intramolecular aldol reaction. The intramolecular aldol reaction was carried out in the presence of one equivalent (S)-(-)-phenylalanine and 0.5 equivalent D-camphorsulfonic acid. The resulting enone was recrystallized from hexane-diethyl ether to yield the product in 43% yield and 98% ee. Since the absolute stereochemistry of the natural product was unknown, the total synthesis also served to establish the absolute stereochemistry. 

Presently, sesquiterpenoids (128, 237, 305, 333, 376) constitute the largest single class of terpenoids, with over 2500 well-defined (only C15) compounds, embracing some 120 distinct skeletal types from acyclic to tetracyclic. Sesquiterpenoids encompass a most impressive array of carbocyclic ring systems, and this diversity and novelty have stimulated outstanding synthetic activity in this field (184). Figure 8.1.8 depicts the important sesquiterpene skeletal types most widely distributed in nature and often encountered as constituents of wood extractives. 

Further work on the sesquiterpenoids of the mushroom species Lactarius has resulted in the isolation of 15-hydroxyblennin A (289) and the four related compounds (290)—(293). " The two ethyl ethers (291) and (293) are almost certainly artefacts of the isolation procedure. Further details of the chemistry of isolactarorufin (294) have been published. The absolute stereochemistry of this unusual tetracyclic compound has not been ascertained as yet. The confusion concerning the precise structures of velleral (295), vellerolactone (296), and pyrovellerolactone (297) has now been firmly resolved by the synthesis of all three compounds as racemates (Scheme 43). 

In concluding this section on the reactions of propargylium complexes with nucleophiles, we note that use of appropriate unsaturated nucleophiles as reaction partners with the cobalt cations or unsaturated electrophiles in the Ade reaction of Co-compleced 1,3-enynes [213-215] offers an efficient route to variously substituted a,(i)-enynes, valuable precursors for intramolecular Pauson-Khand cyclizations (Scheme 4-64) [96, 98]. This tandem methodology has been employed to produce, among others, bicyclo[3.3.0]octenones and their 3-oxa analogs [22, 216, 217], the fusicoccin sesquiterpenoid skeleton [218], linear and angular fused tri- and tetracyclics [219], and fenestrane derivatives [220]. 

Total synthesis of decahydrobenzo[d]xanthene sesquiterpenoids aureol, strongylin A, and stachyflin Development of a new strategy for the construction of a common tetracyclic core structure 13H(87) 2199. 

Formation of cyclopentenes through the RCM of 1,6-dienes can prove itself difficult in very crowded environment. During synthetic efforts toward the tetracyclic skeleton of the sesquiterpenoid tashironin (47), Mehta and Maity reported the efficient RCM of 50 using [Ru]-I that led to 51 in 86% yield [11]. However, the RCM of 52 having a methyl substituent in aUylic position led to 53 in considerably lower yield (25%) even in the presence of the more active [Ru]-II catalyst (Scheme 1.8). 

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