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The rearrangements of dihydrobetulin, dihydrobetulinic acid, and abeo-lupane epoxides under acidic conditions (HCl, montmorillonite K10, and BF3·Et2O) were studied. The treatment of dihydrobetulin with HCl or K10 produced abeo-lupane olefins. Their epoxidation afforded epoxides, which, in the presence of protic or Lewis acids, rearranged to dienes or lupanes bearing a bicyclo[3.3.1]nonane fragment. The structure of final products depended on the nature of the catalyst. The HCl promoted 1,4-elimination of water, whereas in the presence of BF3·Et2O bond migration took place preferentially. Montmorillonite K10 favored cyclization to bicyclononane.

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-homo-28a-thiolupane triterpenes and the corresponding saponins containing D-mannose, D-idose, L-arabinose and L-rhamnose moieties was elaborated. New triterpenes were obtained from readily available 3-O-allylbetulinal by elongation of the carbon chain by Wittig reaction, followed by hydrolysis of the enol ether, reduction of the elongated aldehyde and nucleophilic substitution of the corresponding mesylate with thiocyanate ion. Saponins were obtained by glycosylation of triterpenes with classical Schmidt donors. The cytotoxic activities of the new homothiolupane compounds were evaluated in vitro, revealing that some triterpenes and the corresponding saponins exhibited interesting cytotoxic activity profiles against human cancer cell lines. An unexpected influence of the allyl protecting group on the cytotoxicity of homothiobetulin derivatives was revealed. These results open the way to the synthesis of various lupane-type derivatives containing sulfur in the lupane side chain as potential anticancer compounds.

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 practical method for the preparation of benzoyl protected allyl and benzyl α-D-idopyranosides, and D-idopyranosyl trichloroacetimidate, from 1,2,3,4,6-penta-O-acetyl-α-D-idopyranose, is described. All derivatives can be prepared on a multigram scale and require only simple chromatographic purification. A concise synthesis of lupane triterpenes bearing an unusual D-idopyranoside fragment is described. All new compounds were evaluated in vitro for their cytotoxic activities. Novel saponins exhibited interesting cytotoxic activity in the micromolar range against human cancer cell lines including T-lymphoblastic leukemia CEM, breast adenocarcinoma MCF7, and cervical carcinoma HeLa, but also against normal human fibroblasts BJ.

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 lupane-type saponins bearing OSW-1 disaccharide unit as well as its regio- and stereoisomers were prepared and used for the structure-activity relationships (SAR) study. Unexpected preference for 1→4-linked regioisomers and an unusual inversion of the conformation of the sugar rings were noted. Cytotoxic activity of new lupane compounds was evaluated in vitro and revealed that some saponins exhibited an interesting bioactivity profile against human cancer cell lines. Influence of the protecting groups on the cytotoxicity was investigated. These results open the way to the synthesis of various lupane-type triterpene and saponin derivatives as potential anticancer 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.

Previous studies on the relative reactivity of H2 and tetralin have shown greater hydrogen transfer from H2 to coal than from tetralin to coal at 350 °C. These results are not consistent with a radical pathway for hydrogen addition and require the existence of a nonradical route. We explored the possibility that this nonradical route is synchronous 1,4-H2 addition, which could occur either with acenes or with dihydroxybenzenes. Reactions of Illinois No. 6 coal with added phenanthrene, anthracene, or m-dihydroxybenzene provide no evidence in support of this addition reaction. The 1,4-addition of H2 to phenols produces carbonyl compounds. Reactions of Wyodak coal, which should have a higher population of phenolic groups than Illinois No. 6, show no evidence for a correlation of CO production with H2 utilization or for changes in carbonyl group population that would be consistent with 1,4-addition to phenols. In light of these negative findings, the likely nonradical pathway would then seem to be catalysis b...

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.

Amide-directed hydrocarbonylation of 3-butenamide(1) catalyzed by rhodium complexes such as RhCl(PPh 3 ) 3 , RhCl(CO)(PPh 3 ) 2 , HRh(CO)(PPh 3 ) 3 , and Rh 4 (CO) 12 gives a mixture of 3,4-dihydro-2-pyridone (2), 4-methyl-3-pyrrolin-2-one (3), and a unique heterodimer, 6-(4-methyl-2-oxo-3-pyrrolin-1-yl)-2-piperidone (4)

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

Amide-directed hydrocarbonylation of 3-butenamide(1) catalyzed by rhodium complexes such as RhCl(PPh 3 ) 3 , RhCl(CO)(PPh 3 ) 2 , HRh(CO)(PPh 3 ) 3 , and Rh 4 (CO) 12 gives a mixture of 3,4-dihydro-2-pyridone (2), 4-methyl-3-pyrrolin-2-one (3), and a unique heterodimer, 6-(4-methyl-2-oxo-3-pyrrolin-1-yl)-2-piperidone (4)

The biological activity of bi- cyclic b-lactam antibiotics depends strongly on the absolute configuration of the bridgehead carbon atom. Frelek and co-workers proposed an empirical helicity rule relating the configuration of the bridgehead carbon atom to the sign of the 220 nm band in the elec- tronic circular dichroism (CD) spec- trum of b-lactams. Here we use syn- thetic organic chemistry, CD spectros- copy, and time-dependent density func- tional theory (TDDFT) to investigate the validity of this structure-property relationship for eight model com- pounds. For conformationally flexible b-lactams, substantial thermal effects are found which must be included in calculations. To this end, we combine TDDFT calculations of CD with full quantum-mechanical Born-Oppen- heimer molecular dynamics (MD) sim- ulations for the first time. The CD spectra are sampled with ground-state density functional trajectories of up to 60 ps. The MD simulations show a sur- prisingly high sensitivity of the CD to the molecular conformation. On the other hand, the relation between CD and thermally averaged structural pa- rameters is much less complex. While the helicity rule does not seem to hold for individual conformers, it is con- firmed by the calculations for seven out of eight systems studied if thermal- ly averaged CD spectra and structures are considered. Since thermal effects on CD can be larger than typical inher- ent inaccuracies of TDDFT, our results emphasize the need for a systematic treatment of conformational dynamics in CD calculations even for moderately flexible systems. Temperature-depen- dent CD measurements are very useful for this purpose. Our results also sug- gest that CD spectroscopy may be used as a sensitive probe of conformational dynamics if combined with electronic structure calculations.

A series of polybasic lysine and ornithine derivatives were synthesised as trifluoroacetate salts. Attempts to prepare their free amines according to standard methodology were not successful due to the excellent water solubility of these compounds. Free amines were however efficiently obtained if the column with Diaion HP-20 adsorbent was loaded with the trifluoroacetate and 1% NaHCO(3) aq was passed, followed by elution of free amine with methanol.

The efficacy of a series of dinitroaniline herbicide derivatives for the treatment of Cryptosporidium parvum infections has been studied. The lead compounds oryzalin (compound 1) and trifluralin (compound 2) have low water solubility (C. parvum assays, a result in direct contrast to earlier work with Leishmania . Enhanced water solubility alone did not overcome the drug availability problem; however, several candidates with similar activities but with toxicities lower than those of the lead compounds were produced.

Allyltriphenylphosphonium chloride reacts with some 1-nitronaphthalene and 5-nitroquinoline derivatives in the presence of Ti(i-PrO) 4 and DBU to give 1-hydroxyindoles, which can be reduced in situ to the corresponding indoles.

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)