4,6-Disubstituted quinolizidines structure

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]. 

Although a number of alkaloids belonging to the simple arylquinolizidine class and the lactonic type had been synthesized, no successful synthesis of cyclophane alkaloids was accomplished until that of lythranidine (94), a unique alkaloid with a 2,6-trans disubstituted piperidine structure, was reported (28, 29). Quinolizidine metacyclophane alkaloids lythrancepines II (95) and III (96) have also been synthesized recently (30, 31). A review on the synthesis of lythranidine (94) is available in Japanese (32). 

Over 30 amphibian alkaloids from dendrobatid frogs, bufonid toads, or ranid frogs now are assigned to the 1,4-disubstituted quinolizidine class. For many of these, FTIR data are not yet available. Thus, structural and stereochemical assignments to this class, and the proposed 4,10Z configuration, should be considered tentative for many of these alkaloids. A 4,6-disubstituted quinolizidine class, considered likely by analogy to the... 

Fig. 14. Structures of 1,4-disubstituted quinolizidines from amphibians. All have been characterized only by mass and FTIR spectral properties 73,81)- All have the 4, lOZ configuration. The configuration at the 1 position is as yet unknown.

More recently, the 1,4-disubstituted quinolizidine 275A was reassigned a 4-methyl-9-non)myl-l-azabicyclo[5.3.0]decane structure by comparison with synthetic diastereomers. Fig. (14) [16]. Nevertheless complete characterisation has not yet been reported. 

Fig. (14). Proposed structures of the alkaloid 275A [16] 4,6-Disubstituted Quinolizidines...

All the currently known indolizidine and quinolizidine alkaloids isolated from ants are illustrated in Fig. 6. (+ )-Monomorine I (427), the well-studied trail pheromone constituent of the Pharaoh ant Monomorium pharaonis), and the analogs 428-431 were described in the earlier volumes in this series. These five compounds are 3,5-disubstituted indolizidines bearing short saturated or mono-unsaturated hydrocarbon chains. The relative stereochemistry in monomorine VI (430) still remains unknown, while that of 431 was atypical for the class at the time of its isolation 380). The structural resemblance of fiiis group of alkaloids to the... 

Kobayashi, M., Miyamoto, Y, Aoki, S., Murakami, N., Kitagawa. 1., In, Y, and Ishida, T. (1998) Marine natural products. XXXIX. Isomerization of dimeric 2,9-disubstituted 1-oxa-quinolizidine alkaloids and structural revision of araguspongines B and E from a marine sponge ofXestospor a sp. Heterocydes, 47,195—203. 

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