C20 -Quassinoids

The 5(R)- and 5(,S)-polyandranes (33 and 29), Zus-lactones, were isolated from Castela texana and Castela polyandra [17], respectively, and have been shown by single-crystal X-ray analysis to possess the novel carbon skeleton. In view of the structural similarity between the polyandranes and the C20 quassinoids, it has been suggested that (33) and (29) are derived biogenetically from chaparrinone (226) [134]. 

The second group of C20 quassinoids with a contracted C ring is represented by shinjudUactone and ailantinol D, and the third group with a cleaved C ring is composed of vilmorinines A-F isolated from Ailanthus vilmoriniana (Dode) [6]. 

All six C25-quassinoids now known lack on oxygen function at position 12 but possess one at C-17. This fact substantiates the hypothesis 30,80) that cleavage of the C(13)-C(17) bond to give the much more common C20 quassinoids is triggered by a C-12 oxygen function. 

The C22 and C20 skeletons quassinoids may then be formed by cleavage of the C-13 - C-17 bond while the C19 skeleton compounds require the additional loss of the carbon atom C-16. The Ci8 skeleton results from the C19 skeleton quassinoid by loss of one carbon atom in ring A, presumably due to a benzylic rearrangement resulting in a ring contraction. 

The nematocidal activity of 38 quassinoids, C19 or C20 was measured by using a species of Diplogastridae (Nematoda) to develop lead parasiticides [114], From various quassinoids tested, samaderine B (11) displayed the most potent nematocidal activity with a minimum lethal concentration (MCL) of 2.0 x 10 5 M. 

Several quassinoids are known to have antileukemic activity (Blasko and Cordell, 1988 Cordell, 1978 Polonsky, 1983). Only compounds with a C20 skeleton have antileukemic activity. Quassimarin (51) from Quassia amara and bruceoside A (52) from Brucea javanica and a series of other quassinoids from Brucea antidysenterica (all Simarou-baceae) (Fig. 25.12) are active in this regard. Bruceantin (53) has a high degree of antitumor activity in P-388, LE, LL and B16 tissue culture systems (Cordell, 1978). Six quassinoids from Simaba multiflora and Soulamea soulameoides were shown to be active against several mmor systems (Klocke et al., 1985). 

The three C22 natural quassinoids known in the literature have a butenolide moiety attached to the A ring, presumably originating from the aldol cyclization of a a-acetoxycarbonyl moiety from the normal C20 skeleton. In this series, sergeolide has attracted much attention due to its very good antimalarial potential (Fig. 125.4) [7]. 

These compounds fall into three main categories limonoids, generally tetranor ( 25) compounds with the basic skeleton 514 and those derived therefrom by ring cleavage/cyclization quassinoids, mainly C20 compounds of type 515 and cneoroids, the pentanor C25 compounds with a framework of 516. 

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