Elaeocarpus alkaloids

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

Nitrone cycloadditions may also lead to pyrrolidine according to another type of cycloaddition. The power of the method is illustrated by the synthesis of the peripentadenine intermediate 133 en route to Elaeocarpus alkaloids (Scheme 37) (185). 

A synthetic route to Elaeocarpus alkaloids has been explored. Acylation of the lithium enolate (197) by the benzoyl cyanide (198) gave the diketone (199), which is the key intermediate in a previously reported synthesis of elaeocarpine (Section 3.08.8.2) (79TL1339). 

The use of nitrones in alkaloid synthesis has now been extended to both aromatic and non-aromatic Elaeocarpus alkaloids.5-7 The reaction sequence shown in Scheme 1 gives ( )-elaeocarpine (10) and ( )-isoelaeocarpine (11), and... 

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... 

The ester (3) has been shown to be a useful starting point for the synthesis of Elaeocarpus alkaloids. Ester (3) is converted by several steps into the protected keto-aldehyde (4) this, by reaction with n-propylmagnesium bromide followed by a Jones oxidation of the product and then deprotection, gives the diketone (5). As... 

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... 

Aldol cyclization. Exposure of the hydroxy ketone 1 to excess potassium t-butoxide and benzophenone in refluxing benzene provides the o,/S-unsaturated ketone 2 directly/ This transformation involves a modified Oppenauer oxidation followed by aldol closure of the resulting keto aldehyde. The product serves as an intermediate in the synthesis of Elaeocarpus alkaloids. 

The theimolysis of 2-substituted 2,5-dihydrothiophene 1,1-dioxides leads to ( ) conjugated dienes via cycloieversion followed by the concerted cheletropic extrusion of sulfur dioxide. The thermolysis of the a, -alkylated sulfone (96) gives the intennediate, which loses SO2 to give 1-dodecadien-l-yl acetate (98), a component of the sex pheromone of the red bollwoim moth. Tliis procediue has been extended to the thermolysis of a,3-dialkylated sulfones in order to obtain ( , )-1,4-disubstituted-1,3-dienes (equation 46). Similar processes have been used for the syntheses of alkaloids. The synthesis of an Elaeocarpus alkaloid, elaeokwine A (100), makes use of the retrodiene extrusion of sulfur dioxide to give the 1,3-diene intermediate (99) that is subsequently consumed by an intramolecular imino DA reaction (equation 47). o-Xylylene (102) has been generated by rDA expulsion of SO2 from benzo-fiised 3,6-dihy(ho-l,2-oxathiin 2-oxide (101). ... 

The following post-1986 reviews in this treatise provide the antecedents for several sections of this chapter. The important contribution of Takahata and Momose in Volume 44, entitled "Simple Indolizidine Alkaloids", covered the period 1986 to 1992, but dealt only with Elaeocarpus alkaloids, slaframine, polyhydroxylated indoUzidines such as swainsonine and castanospermine, and alkdoids fiiom ants and amphibians (2). This partial update is especially valuable as a guide to published totd syntheses of these alkaloids. Materi of relevance is also to be found in a number of reviews on more specialized topics. Numata and Ibuka reviewed the chemistry of alkaloids from ants and other insects in Volume 31... 

Another genus, Peripentadenia from north Queensland, produced a series of alkaloids with diverse structures which include peripentadenine (11) (29] and anhydroperipentamine (12) [30], Most of them appear to be related biosynthetically to the Elaeocarpus alkaloids, with the possible exception of the unique isoquinuclidine base, mearsine (13) [31 ]. 

The synthesis of ipalbidine (125), the aglycon of ipalbine, was based on a related approach. The vi-nylogous carbamate (123) was prepared from the V-alkylated thiobutyrolactam (122) via an analogous sulfide-contraction process as described above (Scheme 26). The bicyclic intermediate (124) was generated by selective hydrolysis of the saturated ester followed by immediate treatment with methyl chloro-formate in the presence of catalytic tetrabutylammonium iodide. The bicyclic compound (124) was further elaborate to racemic ipalbidine (125). Parallel applications of this strategy were employed to prepare a series of Elaeocarpus alkaloids (126), (127) and (128) (Scheme 27) as well a benzomorphan analog (129 Scheme 28). °... 

Chart 2. Postulated Biosynthetic Routes to the Elaeocarpus Alkaloids... 

In a further application of this methodology to the Elaeocarpus alkaloid elaeokanine A, Weinreb et al. prepared Diels-Alder precursor 43 (Scheme 2-XV).86,90 On hot tube pyrolysis, compound 43 underwent a cheletropic loss of sulfur dioxide as well as acetic acid elimination to generate an intermediate diene/iV-acylimine, which cyclized to an indoli-... 

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. 

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