Indolizidine alkaloids from amphibians

Fig. 30.13. Simple indolizidine alkaloids from amphibians (modified from Howard and Michael, 1986 used with permission of the copyright owner. Academic Press, Orlando, FL).

INDOLIZIDINE AND QUINOLIZIDINE ALKALOIDS FROM AMPHIBIANS AND ANTS... 

Table 1. Mass Spectra of Newly Identified Indolizidine and Quinolizidine Alkaloids from Amphibians And Ants.

FIO. 7. New quinolizidine, indolizidine, and related alkaloids from amphibians. 

The most common indolizidine and quinolizidine alkaloids from amphibians and ants are usually identified by their GC-MS and GC-FTIR spectral characteristics. These spectral features were collected by Garraffo and co-workers [18,19], and can be summarized as follows ... 

The amphibian alkaloids considered to be 3,5-disubstituted indolizidines are tabulated below. Two other bicyclic alkaloids, proposed as monosub-stituted indolizidines in an earlier review, are included. These are 167B, which was considered likely to be a 5-n-propylindolizidine, based on its mass spectrum and biosynthetic considerations, and 209D, which was considered likely to be a 5-n-hexylindolizidine. These two indolizidines have been synthesized (130,131), but efforts to compare the synthetic indolizidines to natural 167B and 209D were thwarted when the natural trace alkaloids could no longer be detected in extracts. Structures of relatively well-characterized 3,5-disubstituted indolizidines from amphibians are shown in Fig. 11. 

Indolizidine and quinolizidine alkaloids have been found in different natural sources and have been isolated from amphibians, ants, fungi, marine organisms and plants. Most of them have noxious or toxic properties and... 

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... 

Several other general reviews dealing with aspects of indoHzidine and quinolizidine alkaloid chemistry were pubHshed during the period under consideration. The series of annual reports in the Royal Society of Chemistry s journal Natural Product Reports, which provided regular coverage of both simple and various more complex indolizidine and quinolizidine alkaloids, ended in 2008.Another important review that dealt principally with pertinent alkaloids from ants and amphibians, slaframine, polyhydroxy-lated indolizidine alkaloids, and the lupin quinolizidine alkaloids was published in the series Studies in Natural Product Chemistry in 2002, and covered the period 1994 to 1999. ... 

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]. 

Disubstituted indolizidines, unlike many classes of amphibian alkaloids, are not unique to amphibians. 3,5-Disubstituted indolizidines such as monomorine I [(5Z,9Z)-195B] occur in ants of the genera Monomorium and Solenopsis (125,129,134). Some of the ant indolizidines are as follows (5Z,9Z)-3-n-butyl-5-methylindolizidine (monomorine I), (5Z,9Z)-3- -ethyl-5-methylindolizidine, (5Z,9Z)-3-hexyl-5-methylindolizidine, and (5 ,9Z)-3-butyl-5-(4-pentenyl)indolizidine. A series of 5-substituted indolizidines, the piclavines, were reported recently from a marine tunicate (Clavelina picta) (135). 

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