Germacranes

The first report on the Pd(II)-promoted Cope rearrangement is the conversion of fw./ra/w-l,5-cyclodecadiene (44) into c/5-l,2-divinylcyclohexane-PdCl2 complex (45) with a stoichiometric amount of PdCl2(PhCN)2 at room temperature. The complex formation is the driving force of this unusual rearrangement [38,39]. A similar transformation of germacrane (l,5-dimethyl-8-isopropyli-dene-/rfflu,/ra j-l,5-cyclodecadiene) takes place[40j. 

Synthesis of germacrane sesquiterpenoid lactones and related compounds 99T2115. 

P, 5-epoxy-5,10-dihydroxy -6a-angeloyloxy -9(5-isobutyloxy -germacran -8a, 12-olid... 

In one of the earliest applications of this type of process to complex molecule synthesis, Corey and Hortmann, in their synthesis of dihydrocostunolide 38, found that photolysis of 36 afforded a photostationary state of 36 and 37 (Scheme 9)19. Hydrogenation of this mixture then gave 38. A recent modification of this synthesis, which avoids the photostationary equilibrium between eudesmane (36) and germacrane (37) forms, was realized using a modified substrate, 3920. Irradiation of 39 provided a 77% yield of a mixture of diastereomeric ketones 41 these are produced via tautomerization of the intially produced trienol 40. Dienone 41 was then easily converted to 38 via a series of conventional steps (Scheme 9). 

The trans-cis isomerization process observed in the eudesmane/germacrane ring system has been utilized for the synthesis of the c/s-fused sesquiterpene occidentalol, 48a, and its 7-epi isomer, 48b (Scheme ll)22. Photolysis of the traws-fused diene 45 at —78°C afforded triene 46, which upon warming underwent disrotatory electrocyclization to give 47a and 47b as a 1 2 mixture of diastereomers. Apparently, the carboalkoxy group imparts... 

Photocycloaddition of allene to cyclohexenone (341) gave the (3,y-enone (342), which reacted with vinyl magnesium bromide to produce the tertiary alcohol (343) in 79% yield. When the compound (343) was treated with KH and 18-crown-6 in THF at room temperature for two hours and quenched with aq. NH4C1, the cyclobutene (344) was obtained. The thermal ring opening of the cyclobutene (344) proceeded in toluene in a sealed-tube at 180 °C for twelve hours to give a readily separable 5 1 mixture of the civ-olefin (345), and the trans-olefin (346) respectively in 95 % yield. Moreover, (345) could be converted to a mixture of (346) and (345) in the ratio of 10 1 by irradiation. The compounds (345) and (346) possess the skeleton of the germacranes (347), (348) and (349) 122). 

A quite detailed review of transannular cyclizations was published201 wherein their important role in biomimetic syntheses of sesquiterpenes as well as explanation of the biogenetic formation of the polycyclic natural compounds from their monocyclic precursors is discussed. The great significance of these transformations for the synthesis of natural products is also emphasized in a series of reviews which describe the cyclizations to form terpene derivatives, e.g., of the germacrane and humulene systems202-206. 

Vieira, L. et al., Germacranes and flavonoids from Achillea ageratum. Phytochemistry, 45, 111, 1997. 

Brown algae of the family Dictyotaceae yielded diterpenes of the dolabellane, xenicane, crenulide as well as extended germacrane and hydroazulenoid types. Some of these compounds were identified as capable of demonstrating appreciable selectivity as antimalarial agents... 

Recently, germacrene-A (III) has been identified as the alarm pheromone of the sweet clover aphid Therioaphis trifolii (38). This alarm releaser, which has often been proposed as the progenitor of cyclic sesquiterpenes, constitutes the second compound with a germacrane-type skeleton to be identified as an insect pheromone. 

SqSO Atractylon Germacrane Atractylodes japonica TPA, Skin-1 [156]... 

Raucher et al. used a tandem Cope-Claisen rearrangement during total synthesis of the germacrane sesquiterpene (+)-dihydrocostunolide (3)2 (Scheme 1.4c). 

The names periplanone-A and periplanone-B were first coined by Ritter and Persoons in 1974 at the International Congress of Pesticide Chemistry in Helsinki, in a general paper on pheromone research in the Netherlands. In this paper the isolation of a number of pheromones were described, including the two peripla-nones, both sex pheromones, present in the excreta of the female American cockroach, Periplaneta americana. The elementary formulae of these two sesquiterpenoids, C15H20O2 and C15H20O3, were given and the carbon skeleton of periplanone-B, a germacrane derivative, was revealed. Unfortunately, we were informed, one year after the... 

The formation from farnesol of the picrotoxane skeleton of dendrobine (40) has been assumed to involve a 1,3 shift of the l-pro-R hydrogen in the germacrane intermediate (41), although no direct proof of this had been presented. The finding75... 

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