Quassinoids synthesis

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. 

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 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. 

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]/... 

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. ... 

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). 

Lactonization of a b,i-unsaturaled ester/ In a projected synthesis of quassinoid diterpenes, the final step involves lactonization of the unsaturated ester 1. Acid-catalyzed solvolysis (HCl in THE) or treatment with an arvlsulfonic acid in toluene results mainly... 

Manganese triacetate has been specifically reported as a reagent for a -oxidation.Mechanistic dualism analogous to LTA (vide supra) is observed, although the radical process may be more dominant. Watt and coworkers used this technique during the synthesis of quassinoids. Enone (113) was con-... 

A final method of alkene formation from a-derivatized ketones entails formation of unsaturated tosyl-hydrazones from a,P-unsaturated ketones followed by conjugate reduction with sodium cyanoborohy-diide in acid media. This transformation, which proceeds with regioselective migration of the original double bond, has been applied to the synthesis of quassinoids by Ganem et al. (Scheme 22). A similar... 

Melianodiol (66) and its diacetate have been foundin Samadara madagas-caneois (Simaroubaceae), a source of quassinoids. In model experiments directed towards the synthesis of simarolide, melianodiol was converted into the... 

Ring opening of tetrahydrofuran to 4-iodobutanol was used as the starting point for a synthesis of the complex tetracyclic picrasane famework of triterpene quassinoids <050L5601>. Acylative cleavage of tetrahydrofuran can be performed under iodine-... 

This compound was intended to be a model compound for a more complex ketone 207 to be used in the synthesis of the quassinoid natural products, some of which have anti-cancer properties, but, mindful perhaps of Woodward s dictum that the only reliable model compound is the enantiomer of the real thing32 they tried the reaction with 207. With one equivalent of mCPBA they got just one diastereoisomer of the epoxide. 

The rearrangement of 19 - 20, used in the synthesis of the quassinoid bitter principle ( )-amarolide (quassinoids is a generic name for terpenoids having the picrasanc skeleton, which show cytotoxic and antincoplastic properties)604, the rearrangements 0f 21fi05-607 and 22608 609 are further examples of (5,6 rearrangements. 

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

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],... 

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],... 

Various other synthetic studies on bioactive quassinoids have been described in the literature [122-124], such as synthesis of a picrasane-related intermediate from diterpenes constituents from Cupresaceae species, such as Juniperus communis [125],... 

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. 

Attention has been focussed on quassinoids such as glaucarubolone and halacanthone, partly, because they display potent antileukemic activity [137]. This is detailed below the first total synthesis of ( ) glaucarubolone (329) and ( ) holacanthone (330) by Grieco etal. [138]. 

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. 

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