Cis-trans-conversion of the bicycle in pyrrolizidines: The effect of the preferred conformations on the properties of the bases and the thermodynamics of conformational transformation of the ring fusion type. (Review)

Abstract

The cis-trans conversion in pyrrolizidines and the deciding effect of steric factors on their conformational equilibrium are discussed. Work on the synthesis and characteristics of sterically strained pyrrolizidines is analyzed and discussed. It is shown that such compounds (predominantly trans-fused) have a series of features in their properties that greatly distinguish them from unstrained pyrrolizidines. The first results from study of the thermodynamics of cis-trans conversion of the pyrrolizidine bicycle are summarized.

“In Water”: Organocatalyzed Diastereoselective Multicomponent Reactions toward 2-Azapyrrolizidine Alkaloid Scaffolds

“…Pyrrolizidine alkaloids are widespread in nature and possess a noteworthy biological and pharmacological response . Plants containing pyrrolizidine alkaloids are being used as important herbs in TCM, which is popular in China and widely accepted around the world …”

Investigations on 1-azabicycles. 26*. IR spectra of the simplest pyrrolizidine alcohols in the region of the stretching vibrations of the hydroxyl group and their connection with the stereochemistry of the compounds

“…Assignment of the four bands given above to actual cis-(A and C) and trans conformations (B and D) of base 6 requires conducting additional experiments which may be made apparent by the subject of independent experiments. However on the basis of the data of [14,16] it may be expected that in the conformational equilibria (А С) (В D) the overall content of trans-linked conformations B and D will be greater than in the case of the equilibrium between the cis and trans-linked forms of cis-3,8-H-3-methyl-pyrrolizidine (11) [14,15,17]. This is caused by the fact that according to the geometric conditions of forming an IMHB in pyrrolizidine alcohols [1] in the case of compound 6 a conformation of type D obtains additional stabilization in comparison with a conformation of type C as a result of the more stable IMHB in the first than in the second.…”

“…They make it possible to assert that in dilute solution in CCl 4 or tetrachloroethylene the absorption of free and bonded hydroxyl groups are observed in the IR spectra of pyrrolizidine alcohols 1-5 and 7-9. Combination of the data on the weakly conjugated amino alcohols 6 and 8 and the strongly conjugated bases 7 and 9 (the type of conjugation of the bicycle is determined in accordance with [13,14]) enables new information to be obtained on conformational heterogenicity according to the type of coupling of the rings and the preferred conformational state of these substances. Based on the studies on cis-3,8-H-3-alkylpyrrolizidines [14][15][16][17] (10) [14,[16][17][18] it must be assumed that compounds 6-9 exist in the form of cis-(6-9 (A and C)) and trans-linked (6-9 (B and D)) conformations.…”