Elaeokanine

This strategy is successfully applied to the synthesis of the indolizidine framework of an Elaeocarpus alkaloid, (-)-elaeokanine C (Eq. 5) [15,16]. Fur-... 

Both pyrrolizidine and indolizidine alkaloids can be synthesized by taking advantage of the anodic a-alkoxylation of Ai-alkoxycarbonylpyrroKdines (e.g. (131) to (132), Scheme 31). The method has been utilized to synthesize isoretronecanol (137), trachelanthamidine (138), elaeoka-nine A (135), and elaeokanine C (136) [57]. 

Once the methoxy group has been installed and nucleophilic capture of the intermediate has occurred, the product (132) can be treated with an enol ether (e.g. 133) and titanium tetrachloride to affect C-C bond formation adjacent to nitrogen. This sequence served nicely in syntheses of both indolizidine alkaloids elaeokanine A (135) and C (136). 

Iminium ion-vinylsilane cyclizations closely related to the one described here have been used to prepare indolizidine alkaloids of the pumiliotoxin A and elaeokanine families, indole alkaloids, amaryllidaceae alkaloids, and the antibiotic (+)-streptazolin. The ability of the silicon substituent to control the position, and in some cases stereochemistry, of the unsaturation in the product heterocycle was a key feature of each of these syntheses. 

Ni alkoxide as a stoichiometric reaction. However, in this reaction the silylnickel alkoxide 76 is formed, and its reductive elimination affords silyl ethers 77 and 78. At the same time, Ni(0) is regenerated to make the reaction catalytic. The formal total synthesis of elaeokanine C (79) was carried out by this reaction [25], Homoallylic alcohol 81 is obtained by the intermolecular reaction of benzaldehyde with the diene 80 and hydrosilane in high regio- and stereoselective manner [26],... 

An alternative and successful approach to the Elaeocarpus alkaloids has been based on use of the vinylogous urethane (20). This method has led to the synthesis of ( )-elaeocarpine, ( )-isoelaeocarpine, and the ( )-elaeokanines A, B, and C.8 The vinylogous urethane method has been extended to the synthesis of ipalbidine, which is the aglycon of the alkaloid ipalbine.9... 

Nickel-catalyzed cyclization of a 1,3-diene side chain of the substituted pyrrolidones yields a precursor to the indolizidine alkaloid (—)-elaeokanine C (Equation 86) <1997TL3931>. Other metal-catalyzed reactions include the Rh-induced in situ carbene generation and subsequent cyclization onto the heteroatom to yield piperidines <1997T16565, 1997JOC67>. Pauson-Khand cyclizations have also been used (Equation 87) <1997T6611>. 

The protected keto-aldehyde (4) has also been converted, in several steps, into the dihydro-y-pyrones (11) and (12). A Birch reduction of the pyrone (11) with lithium in liquid ammonia afforded ( )-elaeokanine E (13) as the only product. A similar reduction of the epimeric pyrone (12) gave a product that is not identical with elaeokanine D, and it is considered to be ( )-epielaeokanine D (14).4... 

In an alternative approach to this group of alkaloids, ( )-elaeokanine A (9) has been made by an intramolecular imino-Diels-Alder reaction. Pyrolysis of (15) in toluene solution yielded a mixture of the diastereoisomers (16), which, by a sequence of reactions, were converted into ( )-elaeokanine A (9).5 The possible derivation of the Elaeocarpus alkaloids from a common biosynthetic intermediate 3-(l-pyrrolinium)propionaldehyde (17), and the use of (17) in a synthetic approach to these alkaloids, have been discussed.6... 

Wijnberg, B.P, and Speckamp, WN. 1981. a-acyliminium ion synthesis of elaeokanine B. Tetrahedron Lett 22, 5079-5082. 

This methodology was further studied for the total synthesis of the Elaeokarpus alkaloids elaeokanine A (123) and B (122) (80JOC3372 81JA6387). This monoene moiety was prepared in masked form via amide dihydrothiophene dioxide. After O-silylation of methylol acetate 120, the... 

Both pyrrolizidine and indolizidine alkaloids can be synthesized by taking advantage of the anodic a-alkoxylation of A -alkoxycarbonylpyrrolidines (e.g., 83 to 84). The method, first developed by Ross, Finkelstein, and Petersen, and later explored by Ban and coworkers [24, 25], has been utilized by Shono s group to synthesize isoretronecanol (87), trachelanthamidine (88), elaeokanine A (89), and elaeokanine C (90) [26] (Scheme 7). Once the or-methoxy group has been installed via electrooxidation and nucleophilic capture of the intermediate by methanol, the product 84 is treated with enol ether 85 and titanium tetrachloride to affect C-C bond formation adjacent to nitrogen and afford 86. The latter served nicely in syntheses of both indolizidine alkaloids elaeokanine A (89) and C (90). 

Both reaction partners, i.e. the diene and the dienophile, may simultaneously be set free in situ, as illustrated in the total synthesis of the indolizidine alkaloid elaeokanine A (139 Scheme 64).Flash pyrolysis of (136) yields (138), presumably via the nonisolable dieneacylimine (137). 

Simple indolizidine alkaloids from the genus Elaeocarpus were surveyed in Volumes 28 and 44 of this treatise (1,2). The latter survey highlighted a communication on the synthesis of (+ )-elaeokanines A (307) and C (308) by Koizumi and co-workers (289) that has since been published with full experimental details (290). 

No alkaloids had been obtained from the family Elaeocarpaceae until a CSIRO group began a study of certain Elaeocarpus spp. from New Guinea. Amongst a score or so of alkaloids they isolated was a new indole base, elaeocarpidine (7), but most of the others had novel indolizidine structures exemplified by elaeokanine C (8), elaeokanidine A (9) and elaeocarpine (10) [28]. 

Elaeokanine C is also a colourless gum, and is suspected to have the molecular formula C12H21N02, although it has not been subjected to elemental analysis. Its i.r. and n.m.r. spectra are consistent with the structure (18), in which the hydrogen atom at C-7 is equatorial and those at C-8 and C-9 are axially disposed. This gross structure is supported by the reaction of elaeokanine C with ethanolic potassium hydroxide, which affords an a/J-unsaturated ketone having the same retention time on g.l.c. as elaeokanine A.8... 

Elaeokanine D and elaeokanine E, two crystalline alkaloids, are stereoisomers (i.r. and mass spectra) whose n.m.r. spectra are interpreted in terms of the structures (19) and (20) respectively. A sixth alkaloid, elaeokanidine A, contains two nitrogen atoms, but is regarded as a close relative of elaeokanine D in view of the similarity of their n.m.r. spectra. In consequence, elaeokanidine A is formulated as the tricyclic base (21). Finally, two further crystalline alkaloids, elaeokanidines B and C, have been isolated, but not yet extensively investigated. Preliminary data indicate that they are probably stereoisomers of elaeokanidine A. 

The biosynthesis of the elaeocarpine (22) series of alkaloids has been discussed earlier, and it was suggested that they originated from ornithine and a C12 polyketide unit. By analogy it is suggested that the elaeokanine-elaeokanidine series arises by condensation of ornithine with a C8 polyketide component.8... 

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