Stereochemistry of indolizidines

The stereochemistry of indolizidine and pyrrolizidine metho salts was studied by Meyer and Sapianchiay.289 They found that methylation of indolizidine gave a 50 50 mixture of isomers from which only the cis-metho salt could be obtained pure. Cyclization of either 250 or 251 gave only the cis isomer, which can be accounted for on the basis of less... 

The product of the reaction in Entry 8 was used in the synthesis of the alkaloid pseudotropine. The proper stereochemical orientation of the hydroxy group is determined by the structure of the oxazoline ring formed in the cycloaddition. Entry 9 portrays the early stages of synthesis of the biologically important molecule biotin. The reaction in Entry 10 was used to establish the carbocyclic skeleton and stereochemistry of a group of toxic indolizidine alkaloids found in dart poisons from frogs. Entry 11 involves generation of a nitrile oxide. Three other stereoisomers are possible. The observed isomer corresponds to approach from the less hindered convex face of the molecule. 

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. 

In order to assign the stereochemistry of the isomers, indolizidine preparations from 2,6-lutidine (351) by Sonnet (134,435) were employed. The hy-droxyalkylpyridine (392) obtained from 351 was catalytically reduced to afford... 

The 5,8-disubstituted indolizidines and 1,4-disubstituted quinolizidines are the more common structural patterns found in amphibian skin[21]. None of these alkaloids has so far been reported from any other source. In addition, the biological activity of only a few 5,8-disubstituted indolizidines has been investigated due to the isolation in minute quantities from the skin. Among them, the relative stereochemistry of quinolizidine 2071 was anticipated to be 75 by our chiral synthesis of 76[35] followed by stereocontrolled synthesis of 75[36]. A sample of synthetic racemate of 75 had produced the best separations on GC analysis with (3-dextrin chiral column[36]. 

Advances in the Study of the Stereochemistry of Quinolizidines, Indolizidines and Pyr-rolizidines I. M. Skvortsov, Russ. Chem. Rev. (Engl. Transl), 1949, 48, 262-281. 

D NMR studies of stellattamide B allowed the identification of the indolizidine nucleus and of the side chain structure. The relative configuration of the indolizidine nucleus was established by NOESY connectivities and the absolute stereochemistry of the 13 -methyl group was determined via chemical oxidation of the side chain to (S)-2-methylglutaric acid. The nature of the counterion was determined by energy-dispersive spectroscopic experiments. 

M. Vemura et al., ibid., p.4369), although the stereochemistry of the indolizidine unit remained uncertain for some time. 

Elaeocarpine, CieHigOaN (mp 81° [ajj, +0.1°) and isoelaeocarpine (mp 51° [a]u +0.4°) are two new indolizidine alkaloids of a new structural type. The complete structure and stereochemistry of elaeocarpine were determined by X-ray crystal structure analysis of its hydrobromide as LX. Its isomer, LXI, is obtained from LX by treatment with metha-nolic potassium hydroxide at room temperature. Spectral data are in accord with these structures (86). 

There are surprisingly few common approaches to the lupin indolizidines and their quinolizidine homologs despite their structural similarity. One such approach was recently reported by Cutter et al., who used imino—aldol reactions of phenyl 5-chlorovalerate (992) as the starting point for the synthesis of both (—)-tashiromine (ent-929) and (—)-epilupinine (ent-921) (Scheme 123). " The addition of the hthium enolate of 992 to the (S)-N-sulfinylimine (- -)-993 proved to be highly diastereoselective, giving a 78% yield of the adduct (- -)-994 and its (S,S)-isomer (+)-995 in a ratio of 16 1. The stereochemistry of 994 was confirmed by X-ray diffraction. 

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