Eudesmane rearrangement

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... 

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. 

The isoxazolidines derived from aldehydes (17a-b) were converted to eudesmane sesquiterpenes. Thus, quatemization of isoxazolidine (18) was followed by ring expansion via a Stevens rearrangement. 

Reaction of these adducts with a zinc carbenoid is accompanied by a [2,3]-sigmatropic rearrangement of the phenylthio group to generate a new carbon-carbon bond at the original allylic center. This reaction converts 5 stereospccifically into 6, related to eudesmane sesquiterpenes. 

In an attempt to induce a rearrangement to give the pseudoguaianolide (621) the epoxy-alcohol (620) was treated with boron trifluoride etherate. An X-ray analysis, however, has shown that one of the major products is the fluoro-alcohol (622). ° A number of new xanthanolides, grafininacetate (623), desacetyl-xanthanol (624), and xanthanolacetate (625) have been isolated from Pulicaria crispa. These compounds co-occur with the unusual seco-eudesmane sesqui-terpenoid, secocrispiolide (626). 

One interesting facet of the germacrane-type sesquiterpenoids is the conformation of the ten-membered ring. This aspect has previously been discussed in terms of transannular electronic effects (anomalous u.v. spectra) and transannular chemical reactions (Cope rearrangement and cyclisations to eudesmane and/or guaiane types). Recently, the power of two spectroscopic techniques has been brought to bear on this problem. The first of these is the use of the Nuclear Overhauser Effect (NOE) and the second is the A"-ray analysis of a suitable derivative. 

Figure 2.12 also shows how various oxygenation patterns can arise in the eudesmane series and eventually, with the correct pattern, the eudesmane ring structure can rearrange to the vetispirane skeleton. 

Successful application of the Mitsonobu epimerization procedure to an eudesmanic alcohol 44 to bring about inversion of configuration at C(l) is the crucial step in the Harapanhalli synthesis of erivanin (50) from santonin (Scheme 7) [16]. Reduction of enone 43, prepared from santonin in 10 steps, with sodium borohydride furnished the )8-alcohol 44 as the sole product. This product results from the approach of the hydride anion from the less hindered Of-face of the molecule. The chemical modification of the C(3)-C(4) double bond to give a 3a-hydroxy-A4-i4 rnoiety was accomplished via the epoxide 46 and its rearrangement in a basic medium. Epoxidation of 44 with MCPA yielded only one product without any directing effect exerted by the homoallylic alcohol. Treatment of 46 with lithium diisopropylamide (EDA) afforded l-e/>/-erivanin (47). For the synthesis of erivanin (50), epimerization at C(l) prior to the A -modification sequence was required. Attempts to epimerize this carbon atom in 44 by acetolysis of the tosyl derivative 45 were unsuccessful as they led to eliminated product 13 (Scheme 3). 

Of the rearranged eudesmanes, eremophilanes (216) are most prolific ( 150 derivatives). The subject was reviewed in 1977 (314). Two stereochemical classes, 239 and 240, have been recognized in principle, these are related to the eudesmane (222) and intermedeane types (225), respectively. The first member of this class to be characterized was eremophilone (241), which occurs in the wood oil of the Australian tree Eremophila mitchelli, along with other related compounds. This was the first terpene structure not consistent with the isoprene rule and Robinson (327) invoked a 1,2-methyl shift from a eudesmane precursor to rationalize this structure. (-)-Eremoligenol (242) is a component of roots of Ligularia fischeri, while isovalencenic acid (243) has been isolated from vetiver oil. (-h)-Nootkatone (244) was first isolated from the heartwood of Alaska-cedar... 

Valeranone (254) (194), a component of the roots of Valeriana officinalis and of the rhizomes of Nardostachys jatamansi was the first compound to be recognized among a minor group of rearranged eudesmanes in which C-3 methyl (farnesol numbering) has undergone a 1,2-shift. Cryptofauronol (255) is another related compound isolated from Japanese valerian (197). 

Total syntheses of the 1-oxygenated eudesmane sesquiterpenes ( )-dihydro-reynosin and ( )-oxocostic acid have appeared.The ester (166) rearranges to the lactone (167), which is obtained (in good yield) as a 2 1 mixture of epimers at the methyl-bearing carbon (Scheme 95). 

Protonation-induced cychzation of germacrene A generates the cis-decalin skeleton of the eudesmyl cation, an intermediate in the biosynthesis of the phytoalexin capsidiol (79). The eudesmane skeleton is converted to the 5-epi-aristolochene (80) skeleton by Wagner-Meerwein rearrangements of a hydride and a methyl group (Cane 1990). Hydroxylation of 80 then produces capsidiol. The entire process of formation of epi-aristolochene from FPP is mediated by a single synthase which has been purified from tobacco (Starks et al. 1997). The intermediacy of germacrene A in the biosynthesis was demonstrated by mutation of... 

Amazonian species of Emmotum and Poraqueiba two genera of the Icacinaceae family occuring in the Western Hemisphere, contain a class of rearranged eudesmane sesquiterpenes named emmotins that are of higher frequency in (27 compoimds/4 species)... 

Rearranged eudesmane sesquiterpenoids with a 1,4-dimethyl-7-isoprop -decalin skeleton, which we named emmotins, were consistently found in all Ae Emmotum and Poraqueiba species that we have analysed. Other isoprenoids, mainly monoterpenoids and triterpenoids, were also found. 

A fiirther investigation of the trunkwood of the first specimen of E. nitens (Enl) led to the isolation of three authentic eudesmane derivatives, the new emmotinol-A and -B besides the previously known pterocarptriol (24) (Figure 2) and rearranged eudesmane sesquiterpenes, comprising (+)-rishitinol (Table I), a stress compound from Solanaceae (25), and 14 new emmotins represented by 3 tetralones (Table II), 10 naphthalenes (Table III) and 1 naphthoquinone (Table IV) (27). 

Emmotum orbiculatum (Benth.) Miers. The occurence of this small tree is restricted to Amazonas state and the specimen was collected at km 130 of the Manaus - Caracaii road, on sandy soil. The trunkwood afforded three new sesquiterpenoids along with the previously known emmotins-D and -H. The new compounds were characterized as tetralins, two of which, EO-3 and 0-1, were related to the emmotin group, while to the third one ( 0-4) was assigned another rearranged eudesmane skeleton of the l,6-dimethyl-3-isopropyl-decalin type. The... 

Dunham and Lawton have suggested an alternative biogenesis for the eremophilane sesquiterpenes via a series of four decalyl spiro rearrangements, a process which effectively shifts the position of the methyl group from one angular position to the other (238). This proposal has the disadvantage of requiring a cw-fused eudesmane precursor, a known (occidentalol), but rare stereochemical variant, and, at least in the case of capsidiol is excluded by recent biosynthetic results (229). 

The biogenesis of the relatively rare valerane and cyperane (e.g., faurinone and cyperolone) sesquiterpenes involves rearrangement of a eudesmane precursor by shift of the C4 methyl group or ring contraction to a hydrindane nucleus, respectively. Since all of the known natural products bear oxygen functions at the site of rearrangement, an epoxide precursor is usually proposed. 

The co-occurrence of cyperolone (165) with the well-known eudesmane oc-cyperone (163, double bond in place of epoxide) suggests that both may be biosynthesized from a common hydroxy selenadiene precursor 24S). Cyperolone has been synthesized via a biogenetically patterned reaction sequence, the key step of which is rearrangement of epoxy oc-cyperone 163 to hydrindanone 164 (243). 

Hiking, H., T. Kohama, and T. Takemoto Rearrangement of 4,5-Epoxy-Eudesmanes with Boron Trifluoride. Tetrahedron 25, 1037 (1969). 

Mehta, G., G. L. Chetty, U. R. Nayak, and S. Dev Studies in Sesquiterpenes -XXVIII. BFs-Induced Rearrangement of Eudesmane- and 7-Epieudesmane-based 1,2-Epoxides. Tetrahedron 24, 3775 (1968). 

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