Diels-Alder reaction diterpenes

The use of ultrasonic (US) radiation (typical range 20 to 850 kHz) to accelerate Diels-Alder reactions is undergoing continuous expansion. There is a parallelism between the ultrasonic and high pressure-assisted reactions. Ultrasonic radiations induce cavitation, that is, the formation and the collapse of microbubbles inside the liquid phase which is accompanied by the local generation of high temperature and high pressure [29]. Snyder and coworkers [30] published the first ultrasound-assisted Diels-Alder reactions that involved the cycloadditions of o-quinone 37 with appropriate dienes 38 to synthesize abietanoid diterpenes A-C (Scheme 4.7) isolated from the traditional Chinese medicine, Dan Shen, prepared from the roots of Salvia miltiorrhiza Bunge. 

Diels-Alder reaction of the furan derivative 148 with homochiral bicyclic enone 149 is the key step [56] in the total synthesis of the diterpenes jatropho-lone A and B, 151 and 152, respectively, isolated from Jatropha gossypiifolia L [57], Initial efforts to carry out the cycloaddition between 148 and 149 under thermal or Lewis-acid conditions failed due to diene instability. Application of 5kbar of pressure to a neat 1 1 mixture of diene and dienophile afforded crystalline 150 with the desired regiochemistry (Scheme 5.23). Subsequent aromatization, introduction of the methylene group, oxidation and methylation afforded (-l-)-jatropholones 151 and 152. 

Diels-Alder Reaction Dienophiles Difluoroallene Dioxoindoles Dioxolanyliums Discovery of Diels-Alder reaction Discovery of orbital symmetry conservation rule Diterpenes Domino Drtmane sesquiterpenes Compilation 0031, 9804, 9742, 9741. 9737, 9705, 9410, 9406, 9306, 9218, 9118 9126 9705 9833, 9604 9222 9222 0003 0033, 0024, 9835, 9014 9116... 

Recently, Mander and coworkers [122] reported the total synthesis of sordaricin (4-347), the aglycone of the potent antifungal diterpene sordarin which was first isolated in 1971 from the ascomycete Sordaria araneosa. Two approaches were explored the first method utilized a possible biogenetic Diels-Alder reaction the second was based on a domino retro-Diels-Alder/intramolecular Diels-Alder process. Thus, heating of 4-348 led, with extrusion of cyclopentadiene, to a 1,3-butadiene as intermediate which underwent an intramolecular Diels-Alder reaction to give the desired 4-349 as the main product, together with a small amount of 4-350 (Scheme 4.77). 

Diterpene biosynthesis Total synthesis Diels-Alder reaction... 

Diels-Alder catalyst.1 A novel, general route to tricyclic diterpenes involves a Diels-Alder reaction between a hindered diene such as I and a 1,4-benzoquinone. 

Several additional examples of the intramolecular cycloaddition of unactivated acetylenes with isomiinchnones were reported by Maier [30]. This cycloaddition approach represents an efficient method for providing rapid access to annulated furans present in several sesqui- and diterpenes, such as the panicu-lides [51],furanonaphthoquinones [52],furodysin,andfurodysinin [53,54].The decomposition of acyclic acetylenic diazoimides 102 and 103 with Rh2(OAc)4 resulted in cycloaddition and retro-Diels-Alder extrusion of methyl isocyanate to give annulated furans 104 and 105 in good yield. The overall transformation is closely related to the intramolecular Diels-Alder reactions of acetylenic oxa-zoles extensively studied by Jacobi and coworkers [55]. 

A related Diels-Alder reaction offers one approach to the taxane diterpenes. Thus in the presence of (CH,)2A1C1 (3 equiv.) the model compound 3 cyclizes mainly to 4. Even... 

Fascinating rearrangements of aziridines have been applied to the synthesis of diterpene alkaloids by Wiesner and co-workers (Scheme 40). For example, the ester 217, prepared from cyclopentadiene carboxylate (215) and the benzyne precursor 216 by a Diels-Alder reaction, was converted to the aziridine 218 by treatment with benzenesulfonyl azide in 83% yield. When the aziridine 218 was heated with water for 24 h, the hydroxy ester 219 was obtained in 97% yield subsequent oxidation with the Jones reagent afforded the ketone 220. This rearrangement is analogous to that of the benzenesulfonylaziridine of norbomene. ... 

Stypodiol, epistypodiol and stypotriol are secondary diterpene metabolites produced by the tropical brown algae Stypopodium zonaie. These compounds display diverse biological properties, including strong toxic, narcotic, and hyperactive effects upon the reef-dwelling fish. In the laboratory of A. Abad an efficient stereoselective synthesis of stypodiol and its C14 epimer, epistypodiol, was accomplished from (S)-(+)-carvone. The key transformations in the synthesis of these epimeric compounds were an intramolecular Diels-Alder reaction, a sonochemical Barbier reaction and an acid-catalyzed quinol-tertiary alcohol cyclization. 

Hydrophenanthrenes are known to be useful intermediates in the total synthesis of diterpenes and steroids. The Diels-Alder reaction of heteroannular bicyclic dienone 8 with ( )-piperylene (9a) and 2,3-dimethyl-l,3-butadiene (9b)... 

Compound (51) appeared to come from a Diels-Alder reaction between a diterpene diene and ochraceolide A as a dienophile. The possibility of the presence of enzymatic system with hetero or Diels-Alderase activity in Celastraceae was suggested once again, based on the structure of (51)... 

H) Perovskone A Diels—Alder reaction between different types of terpene units is plausible in several cases. Perovskone (55) from the heartwood of Chamaecyparis obtuse s regarded as an adduct between a chiral quinone 53 derived from an abietane-type diterpene (similar to that of grandione) and the linear monoterpene trans-j3-ocimene as shown in Scheme 12. In the total synthesis of perovskone, the Diels-Alder reaction of 53 and trawr-a-ocimene with Lewis acid Eu(fod)3 proceeded in good regio- and... 

Photochemical reactions can produce highly reactive intermediates for subsequent groimd state reactions. Photoisomerization of the cycloheptenone moiety in 151 led to a highly strained trans enol (152) that readily underwent a Diels-Alder reaction with isoprene to produce a mixture of 153 and 154, both of which were carried forward to a structure related to a naturally occurring tricyclic diterpene, vibsanin E (equation 12.94). Irradiation of the aldehyde... 

Other examples of the use of intramolecular Diels-Alder reactions in preparative chemistry have appeared the o-quinodimethane (186), produced as a transient intermediate in the pyrolysis of the analogous benzocyclobutene, cyclizes to give (187 65%), the desulphurization of which (Raney nickel) affords a potential intermediate for the preparation of tetracyclic diterpenes. Elevated temperatures result in the isomerization of (188) into the internal [4 -I- 2] adduct (189) in which it is clear that a cyano-group has acted as a dienophile (189) is the result of a subsequent double-bond shift, and the structure was validated by crystallographic structure analysis. Bridged y-lactams have been successfully prepared by the intramolecular Diels-Alder reactions of NN-diallyl- and iV-(l,l-dimethylprop-2-yn-l-yl)amides of various penta-2,4-diene carboxylic acids. Thus, pyrolysis of (190) gave an 80%... 

Deslongchamps and co-workers approach to the synthesis of Kempane diterpenes employed a ring-closing metathesis strategy in the construction of the 13-membered ring carbocycle, which was subsequently subjected to a transannular Diels-Alder reaction to produce the tricyclic... 

We have thus developed a viable entry utilizing the intramolecular Diels-Alder reaction to assemble a tricylcic ring system which can be cleaved open to the decalin ring system of the Clerodane diterpenes. The approach should also make available highly functionalized decalin derivatives which might he useful for syntheses of other natural products containing a decalin skeleton. 

Several papers have concerned syntheses of terpenoids. The skeleton of sesquiterpenes such as eremophilane has been constructed by Naf etal. from the dienone (45), and Taber and Gunn have described a synthesis of ( )-torreyol (47) as outlined from the enone (46). Wilson and Mao have provided a further paper on their use of the intramolecular Diels-Alder reaction in the synthesis of diterpenes. 

Reaction sequences involving cobalt-mediated [2- -2-f2] cycloadditions and intramolecular Diels-Alder reactions were exploited in synthetic approaches to the basic skeleton of diterpenes of the phyllocladane family (Scheme 7.33) [46] as well as... 

Diels-Alder Reaction and Its Application in the Total Synthesis of Diterpenes... 

The wide diversity of diterpenes has spnrred organic chemists to develop new reactions and innovative tactics. Among them, the pericyclic reactions stood as one the most efficient transformations to generate a wide array of structural diversity. Although the biosyntheses of several diterpenes are not fully elucidated, one can propose that some pericyclic reactions, notably the Diels-Alder reaction, could be involved in these processes. The selected examples in this chapter demonstrate the importance of these transformations in the context of complex diterpene synthesis. Although pericyclic reactions were discovered almost 100 years ago, their use in synthesis is still in its infancy. 

Another means of accelerating cycloaddition reactions that has been investigated is to conduct the reactions at high hydrostatic pressure. Smith reported that the Diels-Alder reaction between furan 26 and enone 27 in various solvents and employing Lewis acid catalysts did not lead to the desired cycloadduct 28 (Scheme 17.6) [24]. The product could, however, be obtained in the absence of solvent at 5 kbar. Adduct 28 was isolated in 80 % yield as a single diastereomer and was subsequently transformed into the diterpene (-i-)-jatropholone A (29). 

These processes are normally enzyme-catalyzed. Purefy ctemical processes are seldom encountered with carbon conq)ounds in nature. The few exceptions include the very act of phenol coupling (by which racemic compounds are obtained), cyclization reactions ofpolyprenyl compoimds (which benefit from the preferred conformation of the reaction partners, suitable for the cyclization, Wendt 2000), and Diels-Alder cycloadditions. The latter have been advocated for the biosynthesis of celastroidine A (= volubilide) from a lupane triterpene and an abietane diterpene in two different plants, Hippocratea celastroides Kunth from Mexico (Jimenez-Estrada 2000) and Hippocratea volubilis Linnaeus (Alvarenga 2000). 

The ABCD ring system of the diterpene alkaloid atisine was constructed by T. Kametani et al using an intramolecular Diels-Alder cycloaddition reaction as the key step. The dienophile was obtained by the traditional Hofmann degradation of the corresponding dimethylamino precursor. The diene was prepared by the kinetic enolization of the cyclohexenone system with LDA. 

Mander and Thomson reported the total synthesis of sordaricin (120), a diterpene isolated from the ascomycete Sordaria araneosa Cain (Scheme 8.19) [51]. Inspired by its biogenesis, they devised a synthetic plan involving a domino retro Diels-Alder/IMDA reaction of a mask cyclopentene 121. Upon liberation of cyclopentene, intermediate 122 underwent an IMDA reaction to give the desired sordaricin analog 123 along with a minor cycloaddnct regioadduct 124. 

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