Of costunolide

A full paper on the cyclization of dihydrocostunolide (341) with aqueous NBS has appeared.a-Cyclocostunolide (342), the product of acid-catalysed cyclization of costunolide, has been converted into santonin (343) by the process outlined in Scheme 54. ... 

CycUzation of costmoKde. Treatment of costunolide (I) with BF3-(C2Hj)20 at room temperature for 1-10 min. affords three products, (2), (3), and (4), in yields of 28,... 

These results, taken in conjunction with the cation-induced cyclizations, indicate that C-l-X (X = H or CCI3) and C-5-C-10 bonding are synchronous. Jain and McCloskey have continued their studies on the cyclization of costunolide (237). On the expectation that the hydroxyeudesmanolide (238), the product of stereospecific hydration of costunolide, might be found in Nature they have prepared... 

The X-ray analysis of the silver nitrate adduct of costunolide clearly shows that the molecule exists as the conformer (204) with the methyl groups in a syn relationship and the double bonds mutually perpendicular. The same features have also been found by the A -ray analyses of the pregeijerene (205)-silver nitrate complex and heavy-atom derivatives of elephantol (206) and shiromodiol (207). ... 

Rodrigues, A. A, Garcia, M., and Rabi, J. A (1978) Facile biomimetic synthesis of costunolide-1,10-epoxide, santamarin and reynosin. Phytochemistry 17, 953,954. 

The bioactivity of costunolide (19) in both the DNA-damaging yeast bioassay and the cytotoxicity assay has led to the suggestion that it acted by interaction with DMA in some manner. The lack of DNA-damaging activity of the structurally related (-)-frullanolide (21) has led to the conclusion that the focus of activity in 19 is not simply the a, -unsaturated lactone moiety as suspected in many other cytotoxicity studies with a-methylene-Y-lactones [32]. 

Cyclization of costunolide. The acid form of Amberlite IR-120 resin was used for a cyclization under mild conditions of the costunolide (1), which polymerizes readily in the presence of strong acids, to a- and -cyclocostunolide, (2)... 

These results indicate that this organism is capable of three different types of biotransformation, including reduction of the a,jS-unsaturated-y-lactone, epoxi-dation, and cyclization. In another biogenetically motivated experiment it has been demonstrated that selenium dioxide oxidation of costunolide (354) proceeds with isomerization of the double bond to produce the melampolide-type compounds (364) and (365). 

Specific examples of the synthesis of natural products containing a-methylene-butyrolactone functions are to be found in the full reports from Danishefsky s group" and from Grieco s group " on the total synthesis of ( )-vernolepin (79) and its isomer, vernomenin Grieco et al. have also reported a synthesis of ( )-desoxyvernolepin " and demonstrated the use of the selenenation method for the introduction of an a-methylene substituent with a neat total synthesis of (+)-costunolide (80) from santonin," together with a general, stereochemically-... 

Cope Rearrangements.—Direct rearrangement of costunolide (197) to dehydro-saussurea lactone (198) is not possible because of the thermal instability of these compounds. However, the a-methylene lactone moiety can be protected as its P-dimethylamino derivative, the rearrangement carried out at 205—2I0°C, and the... 

FIGURE 20.53 Biotransformation of costunolide (165) and its derivative (172a) by Cunninghamella... 

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

Kanasaki, T., and K. Ohta Isolation and Identification of Costunolide as a Piscicidal Component of Marchantia polymorpha. Agric. Biol. Chem. (Tokyo) 40, 1239 (1976). 

The rearrangement of (+)-costunolide, dihydrocostunolide, and (+)-salonitenolide formed the Cope rearrangement products (eqs 193 and 194) and the Pd-initiated carbophilic cyclization products. 

Artemisia maritima is a drug that was widely used in the past as anthelmintic and was later removed based on its severe side effects. Its biosynthesis is based on the methylene reduction of costunolide (23) and its proton activation and cyclization of germacrane core to provide eudesmyl cation (14). Sequential oxidative steps at C-1 and C-3 positions, followed by elimination of water, complete the route to a-santonin [19]. 

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