Elaeokanine synthesis

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

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... 

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 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). 

Elaeokanine C has been synthesized by Hart and co-workers (13) by a route similar to that used by Tanaka and lijima for the synthesis of ( )-elaeocarpine and (+ )-isoelaeocarpine. The diazoketone formed by reaction of %-butyryl chloride with diazomethane was allowed to react with pyrrole in the presence of copper powder to give... 

Eburnane alkaloid synthesis, 54 Elaeokanine A, 63-64 Ellipticine, 303 Enamine, 257... 

In an alternative approach to the nitrone method for the synthesis of Elaeocarpus alkaloids (cf. vol.ll, p.61), a 1,3 dipolar cycloaddition of 1-pyrroline 1-oxlde to a substituted enone gives the isoxazolidine (2), which was converted in a number of steps into the compound (3), the C-7 epimer of elaeokanine C. Oxidation of the epimer (3) afforded the diketone (4), an intermediate in a previously published synthesis of ( )-elaeokanlne C. 

Full details are also available of the structure elucidation of elaeokanines A-E, and elaeokanidines A-C, the leaf alkaloids of E. kaniensis Schltr. further, the structures of elaeokanines A-C have been confirmed by synthesis. The reaction of the diazoketone prepared from butyroyl chloride and diazomethane with pyrrole in the presence of copper powder gave the ketone (9), which was hydrogenated to the basic pyrrolidine ketone (10). Michael addition of ethyl acrylate... 

This synthesis of ( )-elaeokanine C confirms the structure deduced earlier, in particular the cis disposition of hydrogen atoms at C-7 and C-8, since hydrogenation presumably occurs on the enolic form (12a) of the jS-diketone. Curiously, the major product (60%) from this hydrogenation is a crystalline dehydrogenation product, which was assigned the structure (14). 

The Ag- or Pd-mediated intramolecular cyclization of urethanes onto allylic substituents is used in the synthesis of piperidine alkaloids <97JOC776, 97CL221>. Similarly, the tungsten-mediated cyclization of urethanes on alkynes via the metal vinylidene carbene has been reported <97TL7687>. Ni-catalyzed intramolecular cyclization of a 1,3-diene side chain of 5 8 onto an aldehyde affords a precursor to the indolizidine alkaloid (-)-elaeokanine C <97TL3931>. 

This chiral product 5 was used for asymmetric synthesis of the alkaloids (+)-elaeokanine A (9) and (H-)-elaeokanine C (8). Thus the anion of 5 reacts with dimethyl-carbamyl chloride to form mainly the trn/is-amide 6 (97 3). Desilylation (oxalic acid, CH3OH, 96%) and catalytic hydrogenation (96%) provides 7. The dimethylamide group is converted to a propyl ketone by reaction with PrMgCl catalyzed by CeClj (2.5 equiv.) to give (+)-8. Finally, treatment of (+)-8 with NaOH in CH3OH provides (+)-9 in 30% yield. 

An application of the methodology described above to the synthesis of naturally occurring elaeokanine alkaloids was reported by Hua [28]. The chiral, cyclic P-sulfinylenamine (36) was prepared by alkylation-annelation of the a-sulfinylketimine anion of (35) (Scheme 4.19). 

The above synthetic schemes represent the first asymmetric synthesis of these alkaloids as a result, Hua was able to establish the absolute configurations of the natural elaeokanine alkaloids. 

The methodology of McIntosh and Sieler for construction of sulfolenes [83,84] was neatly modified and incorporated in a synthesis of the alkaloid elaeokanine (259) [96]. Ketophosphonate (253) was first condensed with 4-pentenal to give phosphonate (254), which was converted to sulfolene (255). This was transformed into amide (256), which expelled SO2 and AcOH upon heating intermediate (257) cyclized spontaneously to bicycle (258), which was easily converted to elaeokanine (259) (Scheme 6.76). 

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