Ursolic acid-based 24-nor- and A-seco-24-oxy-triterpenoids.

Using methyl 2-cyano-3,4-seco-12(13),4(23)-diene-ursolate as a starting scaffold a series of 3-oxo-24-nor-ursolate and A-seco-ursanes holding hydroxy-, furoyloxy-, p-tosyloxy- as well as aldehyde fragments at C24 that possess cytotoxic activity has been synthesised. The structures of the new ursanes were confirmed by detailed spectral data analysis. The chemoselectivity of methyl 2-cyano-3,4-seco-12(13),4(23)-diene-ursolate oxidation involving the double bond in the A cycle was observed.

An unexpected conversion of 2E-furfurylidene-3-oxo-24-nor-allobetulin to 23-nor-allobetulins.

A series of 2E-furfurylidene-23-nor- and 24-nor-allobetulins has been synthesized by the Claisen-Schmidt condensation and conditions of their formation were studied in detail. It was found that among an expected 2E-furfurylidene-3-oxo-24-nor-allobetulin 4 two byproducts holding 3-oxo-4α-hydroxy- 5 and 3ß,4α-dihydroxy- 6 substituents were formed, which could become the main products under the change of reaction time and amount of the base solution. Moreover, a conversion of individual 2E-furfurylidene-23-nor-3-oxo-4α-hydroxy- 5 into 2E-furfurylidene-23-nor-3ß,4α-dihydroxy-derivative 6 under the treatment with the base solution was observed. An inversion of the configuration at C4 from 24-nor- to 23-nor-allobetulins for compounds 5 - 7 was proved by the NMR spectra. The probable explanation of compound 5 formation includes oxidation by atmospheric oxygen to 4-hydroperoxide, which was further transformed into 4-hydroxy-group. In the presence of the base the reduction C3(=O)-function of compound 5 occurs like Meerwein- Ponndorf-Verley reaction to give compound 6. As a result, a difference in the reactivity of native allobetulin scaffold and 24-nor-allobetulin in the Claisen-Schmidt condensation was observed and a first case of conversion 24-nor- to 23-nor-allobetulin derivatives was described.

24-Nor-allobetulins possess strong α-glucosidase inhibitory activity.

A series of 24-nor-allobetulin derivatives holding 3ß-hydroxy-, oxime, methoxyoxime, lactame and 4-bromobenzylidene substituents have been synthesized and their differences in the NMR spectra were studied in detail. It was revealed that 3-oxo-24-nor-allobetulin loses selectivity in the reaction of oximation and forms a mixture of Z/E oximes (and methoxyoximes) in contract to the related derivatives of native scaffold (that forms only E-isomers). The screening of α-glucosidase inhibitory activity revealed that 24-nor-allobetulins are more active than allobetulins. The lead 3-oxo-24-nor-allobetulin with IC50 0.49 µM was more than 60-fold and 500-fold active than acarbose and 3-oxo-allobetulin, respectively. We can conclude that the removal of the C-24 methyl group significantly increased the antidiabetic effect and 24-nor-allobetulins should be identified as the new and promising scaffolds as α-glucosidase inhibitors on the basis of triterpenoids.