Of quassin

The Dlels-Alder reaction is a favourite way of introducing many chiral centres at once, and we saw examples of this in Chapter 36. Compound (31) was used in a synthesis of quassin." It has seven adjacent chiral centres. How many can bo introduced in one step by a Diels-Alder reaction and what should the starting materials be ... 

A Lewis-acid-catalysed Diels-Alder reaction of the diene (70) and the quinone (71) is the key step in the synthesis of compound (72) with the appropriate stereochemistry and functionality for conversion into quassin.53 The androstane derivative (73) has been transformed into (74) in model experiments towards the synthesis of quassin.54... 

A synthesis of ( )-quassin relies on the AlCh-catalyzed Diels-Alder reaction (292) + (293) (294),... 

The 2-methoxy-4a-methyl-5Q -androst-2-en-l-one system (500), corresponding to the ring a substitution pattern of quassin, has been elaborated from a 5a-androst-l-en-3-one by application of a sequence of familiar transformations.5,6(8-Epoxy-4/3-hydroxy-5/3-cholest-2-en-l-one (501) has been synthesized as a model for rings A and B of withaferin A (502). The synthesis involved multiple steps from cholesta-2,5-dien-l-one related compounds were synthesized from the 2,4-dien-l-one." ... 

This chapter follows the pattern of last year s Report with the addition of a section on Triterpenoid Saponins. The highlight of this year s Report is undoubtedly the total synthesis of /-quassin by Grieco and his co-workers.1... 

Grieco and his co-workers have completed a most notable total synthesis of /-quassin (130) (Scheme 3).1 The synthesis of the hydroxy-lactone (127) was outlined last year (see Vol. 11, p. 121). The conditions developed for the conversion of the bis-(a-hydroxy-ketone) (128) into the bis-(O-methyldiosphenol) (129) also achieved the crucial inversion of configuration at C-9.74 The close proximity of the C-7 oxygen atom to the C-ll carbon atom in the 9-epiquassin skeleton is evident from a series of reactions in which intramolecular participation occurs. Thus, for example, treatment of the epoxide (131) with lithium aluminium hydride gave the ether (132) whose structure and stereochemistry were established by A -ray analysis.75 Synthesis of the tetracyclic (133), a possible intermediate for quassinoid synthesis, involved the intramolecular cycloaddition of a quinonedimethane as the key step.78... 

Quasslae lignum Quassia wood Quassia amara L. SURINAM Picrasma excelsa PLANCH. Simarubaceae MD Secotriterpenes (simariibalides) -0.25% quassin, neoquassin and 18-hydroxy-quassin (0.1%-0J.5%). Bl of the drug, 40000-50000 Bl of quassin/neoquassin, 17 x 10 Fig. 10... 

C Treatment with VS reagent needs at least 15min at 110°C to form the violet-coloured zone of quassin at — 0.65 (vis.), which is accompanied by a blue zone directly above. 

Picrasma exceisa (Sw ) Planch, or of Quassia amara L., Simaroubaceae. The first is known in commerce as Jamaica quassia, the second as Surinam quassia. Habit. Picrasma txelsa inhabits Jamaica and the Caribbeen Islands Quassia amara is a native of Brazil and Guiana and is cultivated in Colombia, Panama, and the West Indies. Quassin and neo quassin are the bitter principles of Surinam quassia picras-min, that of Jamaica quassia. These bitter pinctples are obtained in yields of 0.1-0.296 and appear commercially under the name of quassin. 

In recent years, a number of studies on the synthesis of quassinoids have been reported [126], Among them, total synthesis of quassin (possessing 7 chiral centers) and of castelanolide (possessing 9 chiral centers) both carried out Grieco s group constitute two successful works to synthesize natural quassinoids [1]. Below the main total synthesis of some quassinoids are described. 

This reversal of orientation has been used to prepare (4) in a projected total synthesis of quassin (5), the bitter principle of Quassia amara, which contains... 

Using 3rd instar larvae of the diamondback moth Plutella xylostella), the antifeedant and insecticidal activities of sixteen quassinoids were compared with those of known insect antifeedant chlorodimeform (= galecron), as shown in Table 16. The insecticidal activity of quassin (78) was higher than that of chlorodimeform, although its antifeedant activity was nearly identical to that of the reference compound [39]. 

Q. is used in the food industry as a bitter principle, according to legal regulations brandies may contain up to 50 mg/L Q. as bitter component. Q. has a bitter taste even at a dilution of 1 60 000. In mammals Q. can effect a decrease in heart rate and, at higher concentrations, muscular convulsions and paralyses. The commercially available quassin is a mixture of quassin, neoquassin, isoquassin, and 18-hydroxy-quassin. Q. can be used as a substitute for emetine hydrochloride (see ipecac alkaloids). Some pentacyclic Q. have antiviral, antiparasitic, insecticidal, antifeedant, amoebicidic, and anti-inflammatory activities. 

Small amounts (0.33%) of quassins are produced by callus and suspension cultures of Picrasma quassinoides (Chari wood and Chari wood, 1991). 

With the development of sensitive LC/MS methods, it has been possible to differentiate and make comparative studies as demonstrated in a study with Jamaica quassia (Quassia excels) and quassia extract (P. quassioides) whereby the main constituents isolated were quassin and two isomers of neoquassin however, there was a difference in the minor components. This finding is of significance to evaluate the quality and suitability of the extracts when used as food additives. An ultraperformance liquid chromatography-time-of-flight mass spectrometiy (UPLC-TOFMS) protocol for multiresidue determination of the sum of quassin and neoquassin in strawberry has been developed [107]. 

A combination of column chromatography, ODS HPLC, IR, and NMR, ESI-MS (neg.), and HR-ESI-TOF-MS (pos.) was utilized in isolatirMi two novel quassinoids, delaumonones A (HR-ESI-MS [mJz 531.187 (M + Na) ) and B (HR-ESI-MS [miz 523.2180, (M + Na)" ]) from Laumoniera bruceadelpha [108]. LC ESI-MS/MS has been utilized in the determination of quassin and neoquassin in fruits and vegetables [98] of Q. amara. Limit of determinatirHi (LOD) and limit of quantification (LOQ) for both quassinoids were 0.5 and 1 pg/ kg, respectively, while for picrasinoside B, they were 5 and 10 pg/kg. This study demonstrated that multiple reaction transitions of precursor ions can be used for analytical purposes, and it is possible to detect and quantify quassinoids at trace levels. 

Lang at-Thoruwa C, Kirby GC, Phillipson JD, Warhurst DC, Watt RA, Wright CW (2003) Enhancement of the antiplasmodial activity of quassin by transformation into a gamma-lactone. J Nat Prod 66 1486-1489... 

Mishra K, Oiakraborty D, Pal A, Dey N (2010) Plasmodium falciparum In vitro interaction of quassin and neo-quassin with artesunate, a hemisuccinate derivative of artemisinin. Exp Parasitol 124 421 27... 

Sarais G, Cossu M, Cabras P, Caboni P (2010) Liquid chromatography electrospray ionization tandem mass spectrometric determination of quassin and neoquassin in fruits and vegetables. J Agric Food Chem 58 2807-2811... 

Scragg AH, Allan EJ (1994) Quassia amara (Surinam Quassia) in vitro culture and the production of quassin. In Bajaj YPS (eds) Biotechnology in agriculture and forestry, vol 26. Medicinal and aromatic plants VI. Springer, Heidelberg, pp 316-326... 

Technical advances in structural analysis also initiated subsequent advances in synthesis of quassinoids, leading in particular to the first total synthesis of quassin... 

Clark EP (1937) Quassin. I. The preparation and purification of quassin and neoquassin, with information concerning their molecular formulas. J Am Chem Soc 59 927 Clark EP (1937) Quassin. II. Neoquassin. J Am Chem Soc 59 2511 Clark EP (1938) Quassin. III. Picrasmin. J Am Chem Soc 60 1146... 

The Lewis acid-catalysed orientation reversal in the reaction between substituted cyclohexa-1,3-dienes and 2,6-dimethyl-l,4-benzoquinone ° has been employed in an interesting synthesis of quassin (218). ° Thus, reaction at room temperature of the diene (215) with the above quinone in the presence of an equivalent quantity of Bp3,OEt2 gave the adduct (216) which was converted by several subsequent steps into (218). In the absence of the catalyst the alternative adduct (217) was obtained. Periodic acid oxidation of substituted o-cresols ° and of 2-methoxyphenols in methanol solution affords intermediate o-quinol methyl ethers or o-quinone dimethyl ketals which dimerize to give dienediones with structures related to those of (216) and (217). Another report concerns the formation of a Diels-Alder dimer upon hypochlorite oxidation of 2,2 -methylenebis(4-methyl-6-t-butyl)phenol. ... 

Intermolecular Diels-Alder Routes. The highly oxygenated tetracyclic framework of quassin (53) coupled with its array of stereocentres have made it a formidable synthetic target. However, it has now succumbed to the efforts of Grieco and his collaborators. A Lewis-acid-catalysed Diels-Alder reaction between (50) and (51) generated (52) in which all the stereocentres except that at C-9 have the correct relative stereochemistry. Subsequent functional group manipulation and epimerisation at C-9 served to complete the synthesis. 

Compound (165 a) possesses the complete framework of quassin. Furthermore, with the exception of the configuration at C-9, it has six of the... 

Murae, T., and T. Takahashi Conversion of Quassin into 15p-[(E)-3,4-Dimethyl-2-pentenoyloxy]quassin. A D-Ring Analog of Bruceantin. Bull. Chem. Soc. Jpn. 54,941 (1981). 

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