Formation Of Cleavage Products Research Articles

Chemical methods for the conversion of Prednisolone to 11-β-hydroxy-1,4-androstadiene-3,17-dione

Several microbial transformations of steroids to 17-keto cortisones through side chain cleavage have been presented in the literature; however, yields and product selectivity in these methods were low. In the present study, some new methods have been identified for the side chain cleavage of prednisolone (1) to form 11- β-hydroxy-1,4-androstadiene-3,17-dione (11- β-hydroxy ADD). Prednisolone upon reaction with zinc chloride in dry THF results in the formation of cleavage product in good yield (76%). 11- β-hydroxy ADD (2) has been formed in moderate yield (60%) under the Reformatsky reaction conditions by reacting with zincate. While performing the Wittig reaction using stable ylides, again results in the formation of compound 2 in good yield (56%). Side chain cleavage of prednisolone was confirmed from the physical and analytical data and similar when compared with the literature reports. A few chemical methods were investigated for the side chain cleavage of prednisolone in order to obtain 11-β-hydroxy-1,4-androstadiene-3,17-dione. Among these methods, ZnCl2 mediated transformation gives the best results with 76% yield.

Characterization of a cyanobacterial RNase P ribozyme recognition motif in the IRES of foot-and-mouth disease virus reveals a unique structural element

Translation initiation driven by internal ribosome entry site (IRES) elements is dependent on the structural organization of the IRES region. Picornavirus IRES are organized in structural domains, in which the terminal stem-loops participate in functional RNA-protein interactions. However, the mechanistic role performed by the central domain during internal initiation has not been elucidated yet. Here we show that the foot-and-mouth-disease virus IRES contains a structural motif that serves in vitro as substrate for the Synechocystis sp. RNase P ribozyme, a structure-dependent endonuclease that participates in tRNA precursor processing. Recognition of the IRES substrate was dose dependent, required high magnesium concentration, and resulted in the formation of cleavage products with 5' phosphate and 3' hydroxyl ends. Mapping of the core recognition motif indicated that it overlapped with the apical region of the central domain. Two IRES constructs containing nucleotide substitutions in the apical region of the central domain that reorganized RNA structure displayed an altered pattern of cleavage by the cyanobacterial ribozyme generating new cleavage events in nearby residues. From these data it is inferred that the central domain of the IRES region has evolved a tRNA structural mimicry that renders it a substrate for RNase P ribozyme reaction. Recognition of this motif was affected in defective IRES mutants with a local RNA structure reorganization, suggesting that its structural preservation is required for IRES activity.

Formation of cleavage products by autoxidation of lycopene.

The cleavage products formed by autoxidation of lycopene were evaluated in order to elucidate possible oxidation products of lycopene in biological tissues. Lycopene solubilized at 50 microM in toluene, aqueous Tween 40, or liposomal suspension was oxidized by incubating at 37 degrees C for 72 h. Among a number of oxidation products formed, eight products in the carbonyl compound fraction were identified as 3,7,11 -trimethyl-2,4,6,10-dodecatetraen-1-al, 6,10,14-trimethyl-3,5,7,9,13-pentadecapentaen-2-one, acycloretinal, apo-14'-lycopenal, apo-12'-lycopenal, apo-10'-lycopenal, apo-8'-lycopenal, and apo-6'-lycopenal. These correspond to a series of products formed by cleavage in the respective 11 conjugated double bonds of lycopene. The maximal formation of acycloretinal was 135 nM in toluene, 49 nM in aqueous Tween 40, and 64 nM in liposomal suspension. Acycloretinoic acid was also formed by autoxidation of lycopene, although its formation was lower in the aqueous media than in toluene. The pig liver homogenate had the ability to convert acycloretinal to acycloretinoic acid, comparable to the conversion of all-transretinal to all-trans-retinoic acid. These results suggest that lycopene might be cleaved to a series of apolycopenals and short-chain carbonyl compounds under the oxidative conditions in biological tissues and that acycloretinal is further enzymatically converted to acycloretinoic acid.

Effect of cyclodextrin complexation on photo-Fries rearrangement of naphthyl esters

Photolysis of β-cyclodextrin inclusion complexes of /kl- and 2-naphthyl esters (acetates and benzoates) in aqueous medium, results in rearrangement to give one isomer of acylnaphthol in excess, whereas the solid state irradiation of the cyclodextrin complexes yields selectively one isomer. In addition, formation of cleavage product is totally suppressed. This remarkable selectivity is attributed to specific modes of the complexation of the esters into the β-CD cavity.

Unusual Interactions Between Cleavage Products of a Cis-Cleaving Hammerhead Ribozyme

We have synthesized and tested a cis-cleaving ribozyme designed to have thermodynamically stable stem-loop structures. This cis-ribozyme cleaves very efficiently in vitro, with a cleavage rate of about 0.5/min. Surprisingly, during the course of in vitro transcription and cleavage of our ribozyme, a product of unusual mobility accumulates and coincides with a sharp decline in the rate of formation of cleavage products. Analyses of this electrophoretic variant demonstrated that it is formed by interactions of the cleavage products. Despite the fact that the products and ribozyme transcript are of identical sequence, the cleavage products interact only with one another and not with the uncleaved precursor. This suggests a significant structural difference between the cleaved and uncleaved ribozyme transcripts. Testing of this cis-ribozyme in both yeast and mammalian cells shows no significant cleavage activity in vivo. We conclude that the structure of the ribozyme flanking sequences is important for optimizing the rate of ribozyme cleavage, but this enhanced rate does not necessarily correlate with enhanced in vivo function.

The reaction of dicarbomethoxycarbene with diethyl ether. The mechanism of the formation of cleavage products.

The reaction of dicarbomethoxycarbene with diethyl ether. The mechanism of the formation of cleavage products.

Investigation of the mechanism of the conversion of diols-1,3 in the presence of acid catalysts communication 2. The conversion of pentadiol-2,4,2-methylpentanediol-2,4 and the mechanism of the formation of cleavage products

1. Exhaustive dehydration of pentanediols-2,4 proceeds in stages and stereospecifically with respect to the formation of trans-pentadiene-1,3 (75–100%). Trans-piperylene can be obtained both through the step of the unsaturated alcohol and through the 2,4-dimethyl-β-oxide. 2. Together with dehydration, pentanediols-2,4 undergo cleavage to a substantial degree: on a phosphate catalyst acetone and isopropanol are formed, while on A12O3 acetaldehyde is formed as well. Carbonyl compounds can be formed by isomerization of the dehydration products of the β-oxide or unsaturated alcohol, as well as dealdolization of the intermediate ketol. 3. In the presence of Ca3(PO4)2, cleavage is due to the occurrence of a reaction of hydrogen transfer from the alcohol group of the diol to the carbonyl group of the ketone, resulting in the formation of a ketol, which then undergoes dealdolization. Hydrogen transfer and dealdolization proceed at temperatures (100–150°) at which dehydration of the diol does not take place. 4. In the presence of Al2O3, the degree of cleavage of the diol is lower than on Ca3(PO4)2. Cleavage through the ketol is inhibited by the water liberated as a result of poisoning of the catalyst with respect to the reaction of hydrogen transfer. 5. A general scheme was proposed for the conversions of diols-1,3 on acid catalysts, including reactions of dehydration, isomerization, cleavage, and hydrogen transfer.