Search

Synthesis of lupane bidesmosides was optimized. The title compounds were obtained by glycosylation of 3-O- or 28-O-substituted betulin monodesmosides with Schmidt donors catalyzed by TMSOTf. Classical batch procedure and microreactor technique were used and compared in the above synthesis. Experimental results clearly showed that both methods are comparable, although any particular outcome strongly depends on the structure of the reagents. Undesired allobetulin derivatives formed by the Wagner-Meerwein rearrangement were usually isolated in minute amounts. In the case of batch reaction, shorter reaction time significantly decreased formation of side-products.

Treatment of betulin-type saponins, in which the sugar moiety is connected at the 28-position, with TMSOTf affords 3-O-substituted allobetulin saponins. This unprecedented migration of the sugar part is driven by the Wagner-Meerwein rearrangement of the betulin core. According to our mechanistic studies an oxocarbenium ion released during the rearrangement reacts with the free 3-OH group of the triterpene affording the final allobetulin saponin. Migration rate depends on the size and configuration of the sugar moiety.

Triterpene bidesmosides are considered as highly cytotoxic saponins, usually less toxic against normal cells than monodesmosides, and less haemolytic. Biological activity of the betulin-type bidesmosides, rarely found in Nature, and seldom prepared due to serious synthetic problems, is poorly recognized. We report herein a protocol for the preparation of disubstituted lupane saponins (betulin bidesmosides) by treatment of their benzoates with potassium carbonate in dichloromethane / methanol solution. Cytotoxicity of all compounds was tested in vitro for a series of cancer cell lines, as well as normal human skin BJ fibroblasts. Presence of l -rhamnose moiety is crucial for cytotoxicity of betulin bidesmosides. On the other hand, l -arabinose fragment connected to lupane C-3 carbon atom significantly decreases activity. Presented results clearly show that betulin bidesmosides have significant clinical potential as anticancer agents.

A concise synthesis of 28a-homolupane triterpenes and the corresponding saponins containing d -mannose, d -idose, d -arabinose, and l -rhamnose moieties was elaborated. The overall synthesis of the new triterpenes involved three linear steps starting from readily available 3-O-acetyl-betulinal: elongation of the carbon chain by Wittig reaction followed by enol ether hydrolysis and reduction (or oxidation) of the elongated aldehyde. Saponins were obtained by glycosylation of triterpenes with classical Schmidt donors. Cytotoxic activities of new lupane and homolupane compounds were evaluated in vitro. Several triterpenes and the corresponding saponins exhibited an interesting cytotoxic activity profile against human cancer cell lines. Influence of the side-chain structure and substituents on the cytotoxicity of betulin and homobetulin derivatives was investigated. These results open the way to the synthesis of various lupane-type triterpene and saponin derivatives as potential anticancer compounds.

A concise synthesis of lupane triterpenes with an elongated carbon chain at the C-28 position, as well as saponins containing d -mannose, l -arabinose, and l -rhamnose moieties at the C-3 position is described. The overall synthesis of the new triterpenes involved seven linear steps starting from natural betulin: selective protection of a hydroxyl group, oxidation, elongation of the carbon chain by Grignard reaction, and deoxygenation. O-Glycosides were obtained by glycosylation of triterpenes with classical Schmidt's donors. Additionally, all new compounds were evaluated in vitro for their cytotoxic activities. Several triterpenes and the corresponding saponins exhibited an interesting cytotoxic activity profile against human cancer cell lines. The therapeutical index of active triterpenes is very high, since almost none of them were cytotoxic for normal BJ fibroblasts. These results open the way to the synthesis of various lupane-type saponin derivatives as potentially bioactive compounds.

A series of new (3,4) β-methylenecepham and carbacepham analogues were synthesised as potential antibacterial agents. The key step of the synthesis included presumed generation of the carbene species from the oxalimide substrate effected by triethylphosphite and its intramolecular addition to the double bond. The stereochemistry of the tricyclic system has been elucidated by NMR and X-ray crystallography. In preliminary screening, two of the synthesised compounds exhibited modest antibacterial activity at 1.5–2.0 mg/mL against a number of bacterial strains.

Rhodium-catalyzed silylformylation and amidocarbonylation are applied to the syntheses of pyrrolizidine alkaloids, (±)-isoretronecanol and (±)-trachelanthamidine, from 5-ethynyl-2-pyrrolidinone.

Reactions of hydrosilanes with 1-hexyne catalyzed by Co 2 Rh 2 (CO) 12 , Rh 4 (CO) 12 , ( t BuNC) 4 RhCo(CO) 4 , and Rh(acac)(CO) 2 at 25°C and atmospheric pressure to 10 atm of carbon monoxide give (Z)-1-silyl-2-formyl-1-hexenes ( 1 ), which are the products of “silylformylation”, and/or ( E )-1-silyl-1-hexenes ( 2 ). The ratio of silylformylation vs. hydrosilylation products depends on the electronic nature of hydrosilane used, e.g., PhMe 2 SiH gives 1 almost exclusively whereas (MeO) 3 SiH favors the formation of 2 . When trialkylsilanes such as Et 3 SiH and EtMe 2 SiH are used, the reaction catalyzed by Co 2 Rh 2 (CO) 12 or ( t BuNC) 4 RhCo(CO) 4 gives 2,5-bis(n-butyl)-3-silylcyclopent-2-en-1-one ( 3 ) as a major product, which is a unique silylcarbocyclization product. Mechanism of the formation of 3 is discussed on the basis of deuterium-labeling experiments. Chemoselective silylformylations of alkenynes, a dialkyne, and an alkynyl nitrile proceed in high yields in which alkene and nitrile functionalities are inert for the reaction. Silylformylation is successfully applied to the syntheses of pyrrolizidine alkaloids, (±)-isoretronecanol and (±)-trachelanthamidine, from 5-ethynyl-2-pyrrolidinone ( 6 ) in combination with amidocarbonylation.

The catalytic systems containing the zerovalent tungsten complexes W(CO)6 and (arene)W(CO)3, RAICl2 (R = Me,Et) and molecular oxygen have been investigated in the metathesis of internal and terminal olefins. Besides metathesis, double bond migrations have been found to occur, especially when a terminal olefin was employed as the substrate. Some factors affecting the catalysts' activity and the lifetime of the active centres are described.

Reaction of tetralin in the presence of AlCl 3 and its modifications has been reinvestigated and the products identified. 5- and 6-(1-phenylbutyl) tetralins are the primary products, which subsequently form partly hydrogenated tricyclic aromatic compounds and benzene. Further reactions produce ethylbenzene, n-butylbenzene, ethyltetralins and n-butyltetralins. A catalytic system containing AlCl 3 and hydrated salts (CH 3 COONa·3H 2 O and FeCl 3 ·2H 2 O) has been found to convert tetralin to 5- and 6-(1-phenylbutyl)tetralins with high selectivity.

Synthese selective de l'acide N-phenyl formohydroxamique, par reaction du formaldehyde avec le nitrosobenzene en presence de sels de Co(II) dans differents solvants organiques (acetone, acetonitrile, methanol, nitromethane)