Eudesmanes

Ejudesmane-type sesquiterpenoids are very widely distributed in the Hepaticae, particularly in the Jungermanniales. 

Andersen et al. (7) isolated (+)-a-selinene (326) from Chiloscyphus species. That this substance belonged to the enantiomeric series was established by comparison of its CD curve with those of (—)-a-selinene [=en -(326)] and (+)-5,10-epi-a-selinene (363). The CD spectrum of the latter compound was distinctly different although sign of its optical rotation was also positive. Andersen et al (7) also reported that ORD data in the 

1) (CH2SH)2/BF3-Et20/Ac0H 2) W-2 Raney-Ni/EtOH or MeOH 3) PhaC-Li /DME 4) (CH2Br)2 5) (PhCOO-)2 6) A 450° 7) DBN/CeHg or Toluene 

1) SOCl2/Py 2) OH 3) LiAlH4/Et20 4) Mn02/CH2Cl2 5) Ag20 

1) SOCl2/Py 2) Chromatography on Si02 3) NaHCOa/EtOH 4) Jones 5) NaBH4/MeOH 

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The diastereosclectivity in this particular cyclization was exploited in a number of direct syntheses of terpenes from the eudesmane type (see Table 2). By this technique tricyclic compounds can be synthesized generating three new asymmetric centers55. 

Morikawa, T. Kishi, A. Pongpiriyadacha, Y. Matsuda, H. Yoshikawa, M. Structures of new friedelane-type triterpenes and eudesmane-type sesquiterpene and aldose reductase inhibitors from Salacia chinensis. J. Nat. Prod. 2003, 66, 1191-1196. 

An example, where two C-C-bonds are formed and one C-C-bond is broken is the synthesis of the tricycle 3-285, which has some similarity with the eudesmane framework 3-286, developed by Kilburn and coworkers (Scheme 3.72) [113]. Thus, exposure of the easily accessible methylenecyclopropyl-cyclohexanone 3-281 to samarium(II) iodide led to the generation of ketyl radical 3-282, which builds up a six-membered ring system with simultaneous opening of the cyclopropane moiety. Subsequent capture of the formed radical 3-283 by the adjacent alkyne group afforded the tricycle 3-285 via 3-284 as a single diastereoisomer in up to 60% yield. It should be noted that in this case the usual necessary addition of HMPA could be omitted. 

About two dozen isocyano- and isocyano-related compounds with a eudesmane (12) skeleton are known. Although most of these were isolated from Axinella cannabina, the first isocyanoeudesmane, acanthellin-1 (14) [3], was obtained from a related sponge, Acanthella acuta, (cf. Table 2). Eudalene (13) resulting after two steps (i. Li/EtNH2, . Pd/C) from 14, proved the eudesmane skeleton. 

Both 13C- and H NMR experiments using 2D NMR techniques established that 20 had a cis-eudesmane ring juncture. This was based on a 12% nOe effect between the C-10 methyl and H-5 proton. Based on this and other evidence, the relative stereochemistry as shown in 20 [6a-isocyano-5a-H, 7a-H, 10a-eudesm-4(14)ene] and its analogs (21-22) was proposed [40]. 

The structures and relative stereochemistry of epi-eudesmanes 25-27 from Axinella cannabina were formulated from 2D NMR and chemical correlation experiments [36]. The 500 MHz HNMR spectrum of 1 l-formamido-7/ H-eudesm-5-ene (27) measured in CDC13 showed a 2 3 cis.trans ratio of the -NHCHO group (cis 3 8.06 d, J = 2 Hz trans 5 8.20 d, J — 12 Hz). Isothiocyanate 26 was one of several sesquiterpenes reported from Acanthella pulcherrima [20]. 

Along with epi-eudesmanes, 25-27, alloaromadendranes 58-60 were separated from the chloroform solubles of a methanol extract of A. cannabina [36], As was the case with axisonitrile-2 (53), extensive spectroscopic analyses including Eu(fod)3 shift reagent experiments in XH- and 13C NMR permitted assignment of relative stereochemistry. Acanthella pulcherrima was also a source of isothiocyanate 59, although both isonitrile and formamido compounds appear to be absent [20],... 

The sesquiterpenes (+)-10-epijuneol466, (4.54) and ( )-calameon467) (4.55) have been obtained via addition of 6-isopropyl-3-methyl-2-cyclo-hexenone to cyclobutene derivatives. A similar sequence has been applied for the synthesis of an eudesmane precursor (4.56)468). 

In one of the earliest applications of this type of process to complex molecule synthesis, Corey and Hortmann, in their synthesis of dihydrocostunolide 38, found that photolysis of 36 afforded a photostationary state of 36 and 37 (Scheme 9)19. Hydrogenation of this mixture then gave 38. A recent modification of this synthesis, which avoids the photostationary equilibrium between eudesmane (36) and germacrane (37) forms, was realized using a modified substrate, 3920. Irradiation of 39 provided a 77% yield of a mixture of diastereomeric ketones 41 these are produced via tautomerization of the intially produced trienol 40. Dienone 41 was then easily converted to 38 via a series of conventional steps (Scheme 9). 

The trans-cis isomerization process observed in the eudesmane/germacrane ring system has been utilized for the synthesis of the c/s-fused sesquiterpene occidentalol, 48a, and its 7-epi isomer, 48b (Scheme ll)22. Photolysis of the traws-fused diene 45 at —78°C afforded triene 46, which upon warming underwent disrotatory electrocyclization to give 47a and 47b as a 1 2 mixture of diastereomers. Apparently, the carboalkoxy group imparts... 

The extrapolation of the vinylcyclopropane-cyclopentene rearrangement to a vinyl-cyclobutaiie-cyclohexene synthesis begins to create new insights into the synthesis of six membered ring natural products. The eudesmane sesquiterpene (—)-P-selinene, 217 illustrates such a strategy as summarized in Scheme 14 80). A suitable cyclohexene... 

Fattorusso, E. Santelia, F. U. Appendino, G. Ballero, M. Taglialatela-Scafati, O. Polyoxygenated Eudesmanes and trans-Chrysanthemanes from the Aerial Parts of Santolina insularis. J. Nat. Prod. 2004, 67, 37-41. 

An investigation of the constituents of Mexican species of the genus Eupatorium has resulted in the isolation of sesquiterpenoids belonging to the eudesmane (294a and b), eudesmanolide (295a and b), cadinane (296), and guanolide (297) groups. 

Epoxy-cis-eudesmane (300), the defence pheromone of the West African termite, has been synthesized from lO-epi-y-eudesmol (299) by means of an... 

Chemical and spectroscopic evidence has been provided for the structure of 10-epijunenol (308), a new member of the rare c/s-eudesmane group of sesquiter-penoids."" Rosifoliol, a component of the leaf oil of Australian native raspberry (Rubus rosifolius) has been assigned structure (309) on the basis of its spectroscopic... 

Sesquiterpenoids based on the axane skeleton (354) have been reported previously as metabolites of marine sponges or algae (cf. Vol. 5, p. 77 Vol. 6, p. 89). Further investigations in this area have revealed the presence of axisonitrile-4 (355), axisothiocyanate (356), and axamide-4 (357) in the sponge Axinella cannabina. These compounds are A -derivatives of known metabolites (axisonitrile-1 etc.) of this sponge and are included in this section because their biosynthesis may involve rearrangement of a eudesmane precursor. 

Sesquiterp. dimers elemane/eudesmane macrophyilidimer A and dimeric elemane Inula macrophylla from Uzbekistan Su 2000). 

Sesquiterpenoids isolated form Pluchea indie, Hibiscus tiliaceus, and Thespesia populnea were given full attention. Most sesquiterpenoids isolated form Pluchea indie were eudesmane and eremophilane diterpenoid skeleton, For example, the compounds were depicted in Figure 4. 

The construction of the tricyclo[5.2.0.02,6]nonane (26, n = 1) and tricyclo[6.2.0.02,7]decane (26, n = 2) frameworks involved the [2 4- 2] cycloaddition of readily accessible31,32 l,2-bis(trimethyl-siloxy)cyclobutene and cnone 25, n = 1 or 2, respectively.33 The yields (75-80%) were good for adducts 26a, c, e, and g. Lower yields (40-50%) were observed for adducts 26b and 26f, while adduct 26d was only isolated in a trace amount. The most interesting and important reaction, related to the total synthesis of eudesmane sesquiterpenes, was the photochemical reaction of (-)-piperitone (25g) with l,2-bis(trimethylsiloxy)cyclobutene, which gave c/.v,(5wf/u W-2/j,7/i-dimethyl-4/ -isopropyl-l f ,8Jf -bis(triniethylsiloxy)tricyclo[6.2.0.0z 7]dec-3-one (26g) with the relative cis configuration of the methyl (R2) and isopropyl (R3) groups.33,34 Some of the other photochemical [2 + 2] cycloaddition reactions utilizing l,2-bis(trimethyl-siloxy)cyclobutene are shown by the formation of 2735,36 and 28.37... 

Two further sesquiterpene isothiocyanates were isolated from A. cannabina as minor metabolites. The first (243) is based on the epi-eudesmane skeleton while the next (244) is related to alloaromadendrene [252]. A third isothiocyanate (245) which is a ds-eudesmane derivative... 

The construction of a key intermediate for use in the synthesis of the eudesmane sesquiterpenes starting from 2-methylfuran has been reported (74H(2)639). Metallation of... 

Occidentalol (628), a eudesmane-type sesquiterpene isolated from the wood of Eastern white cedar, was synthesized from a as-fused decalin system (627) prepared by cycloaddition of the a-pyrone (625) with 4-methyl-3-cyclohexenone (626 Scheme 140) (72TL4651). Derivatives of 2-pyrone have also been employed in syntheses of colchicine (629 Scheme 141) (59AG637) and barrelene (630 Scheme 142) (69JA2330). 

These compounds range through monocyclic (with a bisabolane framework), bicyclic (with an eudesmane, amorphane, axane, guaiane, isodaucane, or gorgonane framework), tricyclic (with an aromadendrane, cubenane, maaliane, pupukeanane, or trachyopsane framework), and spiro[4,5]decane carbon skeletons. 

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