Taxodiones, synthesis

SCHEME 8.9 Improved synthesis of taxodione 1 by Motsumoto and coworkers. 

SCHEME 8.10 Engler s synthesis of taxodione 1 via Diels-Alder cycloaddition. 

Besides taxodione and taxodone, these synthetic approaches have been conveniently modified to synthesize other related derivatives such as ferruginols, sugiols, and royleanones.51-52,56-57,60-62 In addition, the enantiomeric-selective synthesis of (+ )-taxodione 1 has been reported using (—)-abietic acid as the starting material63 or with a chiral ligand in the polyene cyclization process.64... 

In addition to the QM structure of the natural terpene QMs, the reactive oxygen species (ROS) may also play a significant role in the observed biological activities. In the synthesis of taxodione and taxodone, QMs were formed from the catechol precursors through the spontaneous oxidation in the presence of silica gel.7, 8,49-51... 

Mori, K. Matsui, M. Diterpenoid total synthesis. XIII. Taxodione, a quinone methide tumor inhibitor. Tetrahedron 1970, 26, 3467-3473. 

Haslinger, E. Michl, G. Synthesis of (+ )-taxodione from (—)-abietic acid. Tetrahedron Lett. 1988, 29, 5751-5754. 

A convenient synthesis of ( )-taxodione, ( )-ferruginol, and ( )-sugiol involved the addition of a substituted benzyl chloride moiety to the aldehyde group of cyclocitral and subsequent oxidation. Cyclization of the product (174) afforded the tricyclic system (175) which was then elaborated further. This... 

ABSTRACT This article reviews the literature published dealing with the synthesis of some bioactive diterpenes. It describes the biological activity and synthesis of only four diterpenes pisiferic acid, camosic acid, triptolide and miltirone. This review excludes the discussions of Taxodione, a bioactive diterpene, because it has already been reviewed [85], The utility of several reagents in the total synthesis of terpenoid compounds has been documented. It can be observed that several routes have been developed for the synthesis of a single diterpene. 

This method has been applied to the synthesis of taxodione and related diterpenes through cyclohexadienone annulations of a chromium-carbene complex which was prepared from a hindered vinyl triflate12lb (equation 99a). 

Polyene cyclization. The catalyst enables an efficient synthesis of precursors of taxodione. It is vastly more effective than BFj OEt2 or other Lewis acids. 

The dimethoxybenzocyclobutenes can be quantitatively hydrolyzed to benzo-cyclobutenones, providing useful functionality in the strained ring. Conversion of 336 to 337 in 79% overall yield provided a key step in the total synthesis of taxodione 338. The synthetic utility of the methodology was considerably extended by providing a good route from the initial cycloadducts to the corresponding benzocyclobutenediones. ... 

ABSTRACT The Wieland-Miescher ketone (1) and its methyl analog (2) have been utilized for the synthesis of several sesquiterpenes like warburganal, muzigadial, albicanol, etc. Similarly several bioactive diterpenes like taxodione, pisiferic acid, aphidicolin, etc., have been synthesized from these ketones. The utility of several reagents in the total synthesis of terpenoid compounds has been documented. The developments of several routes for a single terpene from these ketones have been discussed. 

Taxodione (180), a tumor-inhibitory diterpenoid quinone [70] has been the subject of synthetic endeavours [71] because of its unique structure as a quinone-methide and partly because of its tumor-inhibitory activity. Banerjee and Carrasco [72] developed an alternative synthesis of the ketone (179) whose transformation to taxodione (180) has already been accomplished by Matsumoto [73]. The synthetic route for the synthesis of the ketone (179) is described in "Fig (15)". 

We thank all the people who have provided published and unpublished informations regarding the synthesis of taxodione, pisiferic acid and warburganal, specially Professor T. Matsumoto (Japan) for sending authentic samples of pisiferic acid. We are grateful to Consejo Nacional de Investigaciones Cientificas y Tecnoligicas (CONICIT) and the Institute Venezolano de Investigaciones Cientificas (IVIC) for financial support to carry out some of the work presented in this review. 

A number of major synthetic achievements in the diterpenoid area have been reported during the year. One of these has been the completion of the total synthesis of the insecticidal diterpenoid ryanodol (95) from the two units (93) and (94). The more highly oxidized diterpenoid phenols have attracted attention. Syntheses of the tricyclic phenol cryptojaponol, taxodione, and coleon and approaches to coleon and coleon have been reported. 

Owing to significant by-product formation, aryne [2+2] chemistry is rarely utilized in natural product total synthesis. Nevertheless, several examples exist. In 1982, Stevens and coworkers reported a synthesis of taxodione that utilized [2+2] cycloaddition between an aryne and a ketene acetal (Scheme 7.30). 

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