Quassinoid derivatives

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. 

Table 13. Inhibitory Effects of Quassinoid Derivatives on TPA-induced EBV-EA Activation...

In approaches to a synthesis of quassinoids, the ketone (124), derived from cholic acid, has been converted into the lactone (125), with the C-7 stereochemistry of quassinoids. ... 

Quassinoids.—Simarolide (136) had previously been the only substance providing a structural link between limonoids and quassinoids. The related picrasin A (137) has now been isolated from Picrasma quassioides P. ailan-thoides). It was accompanied in the extract by picrasin B (138) which was converted to quassin (139) by bismuth oxide oxidation and methylation. A series of closely related quassin derivatives, nigakilactones A (140), B (141), C (142), E (143), and F (144) occur with quassin in P. ailanthoides. - The structure of amarolide has been revised to (145). Observation of a large coupling between H-9 and H-11 in the n.m.r. spectrum makes the previous... 

Biogenetically quassinoids can be regarded as degraded triterpenoids and are almost certainly derived from tetracyclic triterpenes. The conversion of the tetracyclic triterpene into quassinoid has been experimentally verified by using labeled mevalonate precursors [3-5] and follows the route originally proposed by Arigoni et ah [6] but extended by further degradation to quassinoids as shown in Scheme 1. 

Problems associated with construction of C(8), C(ll) bridged hemiketal structural array, which is common to numerous naturally occurring quassinoids. To follow is described the synthesis of pentacyclic alcohol (243) which features a protocol for elaboration of ring C functionality found in chaparrinone and related quassinoids A facile five-step sequence commencing with picrasane derivative (237) has been developed for elaboration of the sensitive ring C hemiketal unit chaparrinone (226) (c.f. pentacyclic alcohol 243) [118],... 

Biologically inactive but easily available chaparrin (244) was converted into potent antileukemic C-15 esters of glaucarubolone (245-247) and quassinoid analogs in which C-15 ester side chain has been replaced by an alkyl or alkenyl group. The synthetic methodology developed and described below has been applied to the preparation of C-15 ester derivatives and quassinoid analogs [120],... 

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]. 

ABSTRACT This review covers various bioactive quassinoids in Simaroubaceous plants, which show cytotoxic antitumor, anti-tumor-promoter (= inhibitor against TPA-induced EBV-EA activation), anti-HIV, anti-tuberculosis, insect antifeedant, and other biological activities. Stability of quassinoids, the preparation of their derivatives, and their biological activities are also discussed. 

The same assay was carried out for five semi-synthetic quassinoids, which were obtained by esterification of the C-15 OH group of desacetyl-isobrucein-B (124) as shown in Table 13. All ester derivatives showed higher antitumor promoting activity than that of the starting quassinoid, desacetyl-isobrucein-B (124). A compound containing a fluorinated aliphatic ester showed the highest potency [36]. 

INSECT ANTOHDANT ACnVITY OF NAIIIRAL QUASSINOIDS, THER GLYCOSIDES, AND SEVUSYNTHETIC QUASSlNOfl) DERIVATIVES... 

Camptothecin Derivatives Polyphenolic Compounds and Sesquiterpene Lactones Antitumor Quassinoids Flavonoid Derivatives Colchicine Derivatives Quinone Derivatives... 

Aniineoplasitc agents, Chinese plant-derived camptothecin derivatives, SI cotchicine derivatives, 34 description of, SO flavomiid derivatives, Sl-84 poly enolic compounds, 81 quassinoids, 81 quirtone derivatives. 84-86 sesquiterpene lactones, 81 Antioxjdanis... 

Two major groups of metabolically altered tiiterpenes, the limonoids (tetranortriterpenoids) and the quassinoids (decanortriterpenoids) are derived from euphol (1) (Fig. 25.1) or tirucallol (2) (Fig. 25.2). To date, these compounds are restricted in distribution to the Rutaceae, Meliaceae, Cneora-ceae, Simaroubaceae, and, perhaps, the Burseraceae (Connolly and Hill, 1991), and occur variously in seeds, fruits, and wood of plants of these families. In general, the limonoid and quassinoid content of leaves has not been examined (Taylor, 1983). 

Both limonoids and quassinoids are derived from a cation such as (3) (Fig. 25.2), produced by condensation of a chair-chair-chair-boat configured squalene 2,3-epoxide (4) precursor. By subsequent rearrangement, many other... 

Quassinoids are degraded triterpenes, reported from the members of the Simarouboidaea subfamily of Simaroubaceae. Legend states that a man named Quassi treated fever using the bitter extracts derived from the bark of these trees and hence named quassin [2]. Quassinoids have received attention due to their antiplasmodial, anticancer, and anti-HIV properties. Its efficacy as combinatorial drug coupled with the structure-activity analysis has reclaimed novel structural leads for new drug development. 

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