Quassinoid activity

The synthesis of chaparrinone and other quassinoids (naturally occurring substances with antileukemic activity) is another striking example [16a-c]. The key step of synthesis was the Diels-Alder reaction between the a,/l-unsaturated ketoaldehyde 1 (Scheme 6.1) with ethyl 4-methyl-3,5-hexadienoate 2 (R = Et). In benzene, the exo adduct is prevalent but it does not have the desired stereochemistry at C-14. In water, the reaction rate nearly doubles and both the reaction yield and the endo adduct increase considerably. By using the diene acid 2 (R = H) the reaction in water is 10 times faster than in organic solvent and the diastereoselectivity and the yield are satisfactory. The best result was obtained with diene sodium carboxylate 2 (R = Na) when the reaction is conducted 2m in diene the reaction is complete in 5h and the endo adduct is 75% of the diaster-eoisomeric reaction mixture. 

Quassinoids —The antileukaemic activity of some quassinoids has revived interest in this group. Three new biologically active compounds have been isolated. Quassimarin (118) occurs in Quassia amara with the inactive simalikalactone D (129) 86 Bruceoside A, from Brucea javanica, is the glucoside (120). The third... 

From the seeds and bark of Samadera indica (Simaroubaceae), indaquassin C (296) was isolated together with three additional quassinoids. Only 296, present in 0.006% in seed kernels, exhibited moderate antifeedant activity toward S. litura, with 1 pg leafcm 2, resulting in 48.9% feeding inhibition.128... 

Quassinoids are bitter components produced by members of the Simaroubaceae. They exhibit diverse biological activities including anticancer, antimalarial, insecticidal, and phytotoxic activities. Ailanthone (26), chaparrinone (27), and other quassinoids, along with indole alkaloids, contribute to the invasiveness of the Chinese tree tree-of-heaven Alianthus altissima Swingle), in Europe.15... 

For a recent structure-activity relationship correlation of quassinoids as antitumor agents see M. Okano, F. Narihiko, K. Tagahara, H. Tokuda, A. Iwashima, H. Nishino and K-H. Lee, Cancer Lett. 1995, 94, 139. 

Quassinoids.—The structure of soulameolide (108), a new C25 quassinoid from Soulamea tomentosa, has been established by X-ray analysis.The search for biologically active compounds continues. Undulatone (109) from Hannoa undulata, 6a-tigloyloxychapparinone (110) from Ailanthus integrifoliaj and 6a-senecioylchapparinone (111) from Simaba multiflora have antileukaemic... 

Figure 5 Biological activities associated with quassinoids, from Simaroubaceae species, may not be linked to a common mechanism of action/ Different testing procedures have indicated insecticidal activity for quassin, anticancer activity for quassimarin (also present in Quassia amara) and antimalarial activity for simalikalactone-D/...

Various workers have attempted the chemical 77-80 or microbiological81 modification of quassinoids in the search for compounds with potent antileukaemic activity. 

The highly stereoselective 1,2 rearrangement of allyl vinyl ether 14 gives rise to (3-oxo ester 15 with the correct relative stereochemistry at C-8, C-9, and C-14 of quassinoids (a group of natural products, which exhibit activity against a number of cancer screens e.g., bruceantin), and allows the assembly of rings C, D, and E531. 

QUASSINOIDS STRUCTURAL DIVERSITY, BIOLOGICAL ACTIVITY AND SYNTHETIC... 

For such review the collected data are from 1985 up to 2004 focusing on all the isolated and identified quassinoids, as well as, the main biological activities and some synthetic processes. 

The review containing structural data, biological activities and chemical modifications of quassinoids was published last decade with references up to September 1984 by Polonsky [1]. According to Simao et al. [2] more than two hundred quassinoids were isolated and identified until December 1984. 

Ailantinol G (43) a quassinoid isolated from Ailanthus altissima was evaluated for its antitumor effects promotion against Epstein-Barr virus early antigen activation introduced by 12-0-tetradecanoylphorbol-13-acetate in Raji cells [25],... 

Six quassinoids, named vilmorinine A-F (57-62) were isolated from the cortex of Ailanthus vilmoriniana. The structures were elucidated by various spectroscopic methods, X-ray analysis, and computational chemical methods. Vilmorinines did not show cytotoxic activity (IC50 > 100 (ig/mL) [33-34]. 

Various quassinoids with antileukemic activity have been isolated from the Ethiopian tree Brucea antitfysenterica Mill, including the antileukemic compound bruceantin (234) by kupchan and associates... 

Seeds of Brucea javanica are known as Ya-dan-zi in Chinese folklore and have been used as a Chinese medicine for cancer, and the main active compounds of the plant has been extensively studied and thirty-four quassinoids have thus far isolated the last two decades. 

A new quassinoid, 11 -<9-iram-/ -coumaroyl amarolide (112) isolated from Castela texana and the structure was elucidated by spectroscopic analysis. Compound (112) is the first coumaroyl quassinoid derivative to be isolated from nature [50], Testing in the antimalarial bioassay showed that (112) possessed moderate antimalarial activity without potent cytotoxicity. 

Chaparramarin (113) exhibited moderate insect inhibitory activity against the lepidopteran pest insect, Heliothis virescem (tobacco budworm) [51]. Three quassinoids glycosides, casteloside A (115), casteloside B (116), and casteloside C (117) were also from the bark of Castela tortuosa [53-54],... 

Quassia amara Wood is still widely used in traditional medicine and some quassinoids and quassinoid glycosides isolated from Quassia have received renewed attention due to their biological activity as potential antitumor agents [78]. 

The extracts displayed good activities, while the quassinoids were highly active, with IC50 values very below 1 pg/mL, those chaparrinone (226) and 15-desacetylundulatone (227) being much lower than 0.1 pg/mL (0,037 and 0.047 pg/mL, respectively). 

All four quassinoids were also evaluated in vivo in a standard 4-day test. 15-desacetylundulatone (227) was proven to be the most active compound, almost totally suppressing the parasitaemias of OF1 mice for at least 7 days, while both chaparrinnone (226) and 14-hydroxychaparrinone (228) were active for at least 4 days. 

Quassinoids have EDso values much lower than 50 mg/Kg body weight/day and none of them caused obvious side effects. The keto function at C-2 in 15-desacetylundulatone (227) is apparently of crucial importance for its high activity. 6-a-Tigloyloxyglaucarubol (229) was not active at all. 

Eighteen quassinoids glycosides and nine known quassinoids isolated from Brucea javanica, Brucea cmtidysenterica and Ailanthus altissima were tested for inhibitory activity against HIV replication in H9 lymphocytic cells [103],... 

Likewise, quassinoid shinjulactone A (232) had a good EC50 value of ca. 5 pM but was cytotoxic at this concentration. Shinjulactone B (19) and ailantinol A (43) showed no cytotoxicity and were marginally active with EC50 values of 28 and 30 pM, respectively. 

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