1 -Hydroxy indolizidines

Harris CM, Schneider MJ, Ungemach FS, HiU JE, Harris TM (1998) Biosynthesis of the toxic alkaloids slaframine and swainsonine in Rhizoctonia leguminicola Metabolism of 1-hydroxy-indolizidines. J Am Chem Soc 110 940-949... 

Aaron s group has studied various hydroxy derivatives of both indolizidines and pyrrolizidines and assigned conformations, mainly on the basis of infrared data. The isomers of 8- (240, 241) and 7-hydroxy-indolizidine (242, 243) were separated as racemates after chemical or catalytic reduction of the ketones.282... 

Cinnolin-4(lH)-one, 8-hydroxy-iodination, 3, 21 Cinnolin-4-ones synthesis, 3, 56 Circular dichroism indolizidines, 4, 450 pyridines and benzo derivatives, 2, 126... 

Indolizidine, 6-(3-furyl)-8-methyI-occurrence, 4, 477 Indolizidine, hydroxy-basicity, 4, 461... 

Indolizidine, 1 -hydroxy-2-methyl-synthesis, 4, 471 Indolizidine, 1-hydroxy-3-oxo-benzoylation, 4, 461 Indolizidine, 3-methyl-synthesis... 

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. 

Daly, J. W., Tokuyama, T., Fujiwara, T., Highet, R. J., Karle, I. L. A new class of indolizidine alkaloids from the poison frog, Dendrobates tricolor. X-ray analysis of 8-hydroxy-8-methyl-6-(2 -methylhexylidene)-1-azabicyclo[4.3.0]nonane, J. Am. Chem. Soc. 1980, 102, 830-836. 

An important new route to indolizidine starts from 2-(3-hydroxy-propyl)tetrahydrofuran, which is converted via the chloro and cyano compounds into the amine. This is then cyclized to indolizidine in good yield with an alumina/zirconium dioxide catalyst. The 6-methyl derivative has also been prepared as a mixture of isomers from 2-(3-hydroxy-butyl)-tetrahydrofuran.233... 

Two classes of simple indolizidines have been characterized from amphibians. These are in addition to the more complex pumiliotoxin-A class of indolizidines where 8-hydroxy, 8-methyl, and 6-alkylidene substituents are present in the indolizidine ring (see Section III,C). The simple indolizidines are either 3,5- or 5,8-disubstituted. However, the existence of 3- or 5-monosubstituted indolizidines also has been postulated. 

Treatment of 2,3 Cpoxy-l-amines with Lewis acid induces a rearrangement to aziridinium ions that react efficiently with a nucleophiles to give functionalized hydroxy sulfides or hydroxy amines (Equation 23) <1997SL11>. Under the influence of ethylaluminium chloride, an epoxide tethered to an azide undergoes Lewis acid-assisted cyclization followed by an intramolecular Schmidt reaction and subsequent in situ reduction of the intermediate iminium species upon addition of sodium borohydride (Scheme 8). This protocol was used as a key step in a novel synthesis of indolizidine alkaloids of pharmaceutical interest <20030L583, 2004JOC3093>. 

Hapepunine (72), occurring in Fvitillavia aamtsahataensis, is the first natural 166-hydroxy-22,26-epiminocholestane derivative encountered (Mitsuhashi et al., Tetrahedron Letters, 1978, 2099). Anrakorinine, from the same source, affords a tosylate which on reduction (LiAlH ) yields hapepunine (72). In its pmr-spectrum it lacks a methyl singlet at 6 0.96 ppm (present in hapepunine), but has an AB quartet (2H) at 3.62 and 3.88 ppm. Consequently it is formulated as 18-hydroxyhapepunine (73) idem, Phytochem., 1981, M, 157). Several indolizidine bases, also related to Solarium Alkaloids, have been encountered in the Fritil-laria group. Camtschatcanidine, for example, from F. aamtsohatoensis, is (74), on the basis of spectral comparison with solanidine on reduction (LiAlHi ) of its 0-tosyl-derivative solanidine (75) is formed (Mitsuhashi et al.. 

Synthesis of (—)-Laulimalide. Different approaches to the (3-hydroxy sulfone moiety needed for the olefination reaction are frequently used in the synthesis of natural products. For instance, a very common strategy consists of carbonyl reduction of the corresponding a-ketosulfone followed by reductive elimination. This sequence is employed in the synthesis of polyhydroxylated indolizidine alkaloids (Eq. 121),207 (+)-dihydromevinolin,268 pleraplysillin-1,269 amphidino-lide B,270 and the novel antitumor agent (—)-laulimalide (Eq. 158).271... 

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