Quassinoids total synthesis

Fleck TJ, Grieco PA (1992) Synthetic studies on quassinoids total synthesis of ( )-glaucarubolone and ( )-holacanthone. Tetrahedron Lett 33 1813-1816... 

Grieco PA, Collins JL, Moher ED, Fleck TJ, Gross RS (1993) Synthetic studies on quassinoids Total synthesis of (-)-Chaparrinone, (-)-Glaucarubolone, and (-1-)-Glaucarubinone. J Am Chem Soc 115 6078-6093... 

The efforts at quassinoid total synthesis can be summarized as follows ... 

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]/... 

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). 

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... 

The mild and efficient method detailed above for the elaboration of the sensitive C/E ring system of chaparrinone (226) and glaucarubolone should prove exceedingly useful in total synthesis quassinoid [118],... 

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. 

The total synthesis of ( )-amarolide (267), a quassinoid having 10 chiral centers, was accomplished from the previously reported 12 3-hydroxy-pricasan-3-one (259) by 18 step reactions. The synthetic strategy applied by Hirota et al. [129] is outlined above. 

The total synthesis of the quassinoid shinjulactone C (341) is detailed above, which proceeds via pentacyclic lactone [140] and... 

Since the isolation and characterization of bruceantin (234) by Kupchan and associates over 30 years ago [104], synthetic organic chemists worldwide have been engaged in efforts to prepare (234) and closely related quassinoids via total synthesis. 

Hirota, in the total synthesis of quassinoid amaroUde 257 [56], used a nonacidic catalysis with pentachlorophenol. Under these conditions and in the presence of 4 A molecular sieves, the expected ester 259 was obtained in moderate yield. However, large amounts of starting material were recovered. The diastereo-... 

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

More than ten years have elapsed since the publication of a comprehensive review on the quassinoids, the bitter principles of the Simaroubaceae family (80). Interest in these terpenoids has increased enormously in recent years due in part to the finding of the American National Cancer Institute in the early 1970s that these compounds display marked antileukemic activity. Furthermore, a wide spectrum of other biological properties for the quassinoids has been discovered and studies on chemical modifications of inactive members to yield biologically active ones were undertaken. New structures have been established also and numerous synthetic approaches have been developed which include the total synthesis of the parent compound, quassin (p. 250) and also that of castelanolide (p. 253). 

The broad spectrum of biological properties, especially the antileukemic activity, of the quassinoids as well as their highly oxygenated carbon backbone coupled with the stereochemical features have stimulated a great deal of synthetic activity. A number of approaches towards their synthesis have been described, but success at total synthesis has so far been limited to only two published accounts (vide infra). 

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