Racemic elacomine ((%)-2), a hemiterpene spiro oxindole alkaloid from Elueagnus commutata, was synthesized in five steps from 6-methoxytryptamine (19) in 16% overall yield (Scheme 3 ) . The final oxidative rearrangement of the corresponding 8-carboline precursor (%)-21 furnished isoelacomine ((%)-22) as a by-product (6% overall yield). A more elaborate route that started from L-tryptophan furnished (+)-2 and (-)-22 with optical purities of 76% (Scheme 4 ) and established the absolute configuration of these compounds. A reinvestigation of the alkaloidal content of the roots of E. cornmututu showed that both elacomine and isoelacomine occur naturally in racemic form. ( [ a ] , = +174.8) hemiterpene oxindole alkaloid3) from the roots of the shrub Elaeagnus commutata (Elaegnaceae) [ 11. Chemical degradation studies and spectroscopic evidence led to structure proposal 1 which, however, left open the exact position of the phenolic OH group and the relative configuration at the two asymmetric centres C(3) and C(4')4). These questions were addressed subsequently by James and Williams by means of an X-ray diffraction study that allowed them to established formula 2 for this compound which they had obtained from Locock and Slywka [2]. Curiously enough, the sample investigated by X-ray crystallography must have been racemic, since the crystal was composed of alternating layers of both optical antipodes of 2, a fact that is consistent with the reported space group P2,lc. Surprisingly, the evident conflict concerning the enantiomeric purity of 2 was not commented by James and Williams, and in the context of our interest in the chemo-and diastereoselective transformation of indole alkaloids into their oxindole (1,3-dihydro-2H-indol-2-one) or pseudoindoxyl (1,2-dihydro-3H-indo1-3-one) derivatives [4-81, we decided to synthesize (+)-elacomine ((+)-2) in a way that would allow to delineate its hitherto unknown absolute configuration. Introduction. ~ In 1968, Slywka reported the isolation of a novel, optically active

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The racemic form of the bicyclic diterpene hydrocarbon 6 -araneosene (4), endowed with the dolahellane skeleton, was prepared from geraniol in two different ways. The more efficient route involved 13 steps and proceeded with an overall yield of 3.6% (average: 77% per step). With this reference sample at hand, the hitherto elusive metabolite (-)-4, a likely biogenetic precursor of cycloaraneosene ((-)-3) and sordaricin ((-)-1), could finally be isolated in 2 99.5% purity from the neutral fractions of the mold Sorduriu uraneosu CAIN (Ascomycetes).

SummaryAn improved method for obtaining optically pure (S)-( 1-p -menthen-8-yl)amine (12) has led to expedient syntheses of two hypothetical biogenetic intermediates on the way to aristoteline (7), namely (S)-N-(l-p-menthen-8-yl)-2-(3-indolyl)ethylamine (3) and (S)-N-(l-p-menthen-8-yl)-2-(3-indolyl)ethylideneamine (4). The latter has been transformed into (-)-hobarthe (6) in 64 % yield via a stereoselective biomimetic cyclization by treatment with HCOOH. This unambiguous synthesis establishes the hitherto unknown absolute configuration of (-)-hobartine (6). Several model cyclization reactions of N-substituted a -(terpen-%yl)imine derivatives yielding unsaturated 3-azabicyclo-[3.3. llnonane compounds are described. Aristoteline (7) was isolated in 1975 by Bick et al. [l] from the New Zealand plant Aristotelia serrata as the first member of a novel group of indole alkaloids. The same authors determined its pentacyclic structure by X-ray crystallography. Subsequently, this natural product was detected in other plants [2] [3] together with several related alkaloids'), of which two, the tetracyclic compounds makomakine (5) and hobartine (6) (Scheme I ) , are on the same oxidation level as aristoteline (7).The outstanding feature of this alkaloid family is that most of its members embody an intact monoterpene unit, whereas the vast majority of the known mevalonoid indole alkaloids originate from secologanin which arises from an oxidative cleavage of a preformed cyclopentane monoterpene. (cf. e.g. [ 141 and ref. therein). A plausible pathway to the aristoteline family has been proposed by Bick et al. [15] and, in a slightly modified version, by Hesse et al. [3]. Their proposal which is relevant to the present discussion is shown in Scheme I :According to Scheme I cyclization of nerylpyrophosphate (2) in the presence of tryptamine (1) leads to 3 as the first biogenetic intermediate containing all C-atoms of the aristoteline-type alkaloids. To date, this compound has not been detected in natural sources, but an oxidized version of its skeleton is present in frutico-') Presented in part at the 'Herbstversammlung

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The total synthesis of (+)-ryanodol (1) is described.

The methanolysis of the epimeric 7-chloro-7H-yohimbine derivatives 2 and 3 was reinvestigated. In case of the 7a-epimer 2, the reaction was uneventful and conformed with earlier observations, i.e., under sufficiently mild conditions, only the imino ether 4 ( = imino ether A) was produced. Under the same conditions, the less reactive p-isomer 3 furnished a mixture of both imino ethers 4 and 5, accompanied by the elimination product 11, and by equal amounts of yohimbine (1) and 3,4,5,6-tetradehydroyohimbine (12), which are believed to arise through a disproportionation process of the putative intermediate 5,6-didehydroyohimbine (23). The nature of this divergent reactivity and of the ready equilibration of 4 and 5 was investigated by means of extensive force-field and semi-empirical calculations (AM1 and PM3) of various conformers of the compounds 2-5 and of some possible reaction intermediates.

The synthetic efforts of the author's research team in several areas within the monoterpene indole alkaloid family are summarized. Most of the work was accomplished in the field of the Aristotelia alkaloids, where some 25 natural products were synthesized for the first time. Systematic investigations on the oxidative rearrangement of indoles to oxindoles and pseudoindoxyl derivatives led to control over the chemoselectivity and stereoselectivity of this process, which served for enantioselective preparations of the simple alkaloids horsfiline and elacomine. In addition, recent developments in a novel approach to Iboga alkaloids containing a hydroxyl group at C(19) are presented. The key steps involved a self-immolating 1,4-chirality transfer in an Ireland-Claisen rearrangement and an intramolecular nitrone-olefin [2+3]-cycloaddition to give the aliphatic isoquinuclidine core of the target molecules. The first synthesis of (19R)hydroxyibogamine was completed by grafting a 3-ethylindole unit onto the aliphatic nitrogen, followed by closing the 7membered ring.