Quassinoids

Quassinoids.—Soulameamuelleri (Simaroubaceae) has yielded soulameanone (120), 1,12-di-O-acetylsoulameanone (121), and A2-picrasin B (122). The structure of (120) was established by X-ray analysis. Treatment of (122) with diazomethane afforded quassin.70 Other new quassinoid natural products reported this year are soularubinone (123), an antileukaemic compound from S. tomentosa,71 13,18- 

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

Kametani, M. Chihiro, T. Honda, and K. Fukumoto, Chem. Pharm. Bull., 1980, 28, 2468. 

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 

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 

Hikino, T. Ohta, and T. Takemoto, Chem. Pharm. Bull. Japan), 1970, 18, 1082. 

Tsuyuki, T. Nishihama, S. Masuda, and T. Takahashi, Tetrahedron Letters, 1969, 3013. 

11-one, 12-ol assignment untenable. The structure (146), previously suggested for bisnorquassin, has been confirmed in detail by an X-ray analysis which also revealed the stereochemistry.  

The recently found quassinoids will be presented according to their basic skeleton and when relevant comment will be made on the specific biological activity of the individual compounds. 

Samaderine A (1) isolated from Samadera indica 111), laurycolactone A (2) and B (3) isolated from the Vietnamese Simaroubaceae Eurycoma longifolia Jack 67) are the only three Cig-quassinoids so far known. The structures of (1) and (2) were established by X-ray analysis and that of (3) by spectral evidence. 

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Note that this method does not work on simple esters. In addition, TMSOCH2CH2OTMS/TMSOTF has been used to effect this conversion.The same process was used to introduce the cyclohexyl version of this ortho ester in a quassinoid synthesis. Its cleavage was effected with DDQ in aqueous acetone.(R,R)-2,3-Butanediol can be used to resolve the lactone. 

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. 

An intramolecular lactonisation features as the final stage in an enantiospecific assembly of the pentacyclic quassinoid framework <96CC2369>. 

Isolation of two quassinoids (quassin and simalikalactone D) from root bark of Quassia africana Baill... 

Spino and colleagues134 studied the Diels-Alder reactions of vinylallenes aiming to synthesize six-membered rings with a tetrasubstituted exocyclic double bond, which were to be employed as precursors of quassinoids. Some representative results of their investigations have been summarized in Table 5 (equation 56). Due to the presence of two different substituents at the allene terminus of 200, facial differentiation occurred, which resulted in non-equivalent amounts of geometrical isomers 201 and 202. The major isomers obtained in each case were formed by endo attack of maleic anhydride 144 at the less hindered face of the diene. 

Nakata showed that stoich. RuOyCCl oxidised steroidal diols to the corresponding ketones [237] electrogenerated RuO from RuO /aq. NaCl/Na(H3PO ) pH 4/ Pt electrodes converted diols to lactones and keto acids (Tables 2.1-2.4) [267] and RuCyaq. 10(0H)3/CC1 -CH3CN oxidised 3-(benzyloxy)-l,2-octanediol to the acid (Tables 3.4, 3.5) [107]. A diol was converted to a lactone by stoicheio-metric oxidation with RuOyCCl as part of the total synthesis of the quassinoid ( )-amarolide [82],... 

A diol was converted to a lactone by oxidation with stoich. RuOyCCl as part of the total synthesis of the quassinoid ( )-amaroMe [355] stoich. (PPh )[Ru(0)2Cl3]/... 

T riterp. azadirachtin-like tetranortritero. azadirachtin (neem teee,Azadirachta indicaA. Juss., Meliaceae, Ang. MI) Quassinoids (biosynthetically related to triterp.) including seco- and further degraded forms Quassia amara L., Sapindales, Ang. from Jamaica quassin DSII, and other metabolites Connolly 1997). 

N.A. Quassinoids, ailanthone, quassin, alkaloids, flavonols, tannins." Antimalarial, against cancerous cells, counter worms, excessive vaginal discharge, gonorrhea, malaria, antispasmodic, cardiac depressant. 

N.A. Picrasma exeelsa (Sw.) Planch. Quassinoid (quassin), alkaloids, coumarin (scopoletin), vitamin B,.09 Strengthen digestive systems, increase bile flow, secretion of salivary juices, and stomach acid production. 

Polyphenolic Compounds and Sesquiterpene Lactones 62.2.3 Antitumor Quassinoids... 

J. Herscovici, S. Delatre, L. Boumaiza, and K. Antonakis, Stereocontrolled routes to functionalized [1,8-bcJ-naphthopyran—a study on the total synthesis of quassinoids and tetra-hydronaphthalene antibiotics, J. Org. Chem. 58 3928 (1993). 

The novel chloroenone quassinoid eurycolactone B (444) was characterized from the roots of Eurycoma longifolia from Malaysia (629). This is the first halogenated quassinoid discovered in a plant. A series of norditerpene dilactones, including the chlorinated rakanmakilactones E (445), G (446), and 447, were isolated from the leaves of Podocarpus macrophyllus from Japan (630, 631). These represent the first halogenated norditerpene dilactones found in the Podocarpaceae. 

Coombes PH, Naidoo D, Mulholland DA, Randrianarivelojosia M (2005) Quassinoids from the Leaves of the Madagascan Simaroubaceae Samadera madagascariensis. Phytochemistry 66 2734... 

Ang HH, Hitotsuyanagi Y, Takeya K (2000) Eurycolactones A-C, Novel Quassinoids from Eurycoma longifolia. Tetrahedron Lett 41 6849... 

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