Chemo-enzymatic synthesis of 4-methylumbelliferyl beta-(1-->4)-D-xylooligosides: new substrates for beta-D-xylanase assays

Transglycosylation catalyzed by a beta-D-xylosidase from Aspergillus sp. was used to synthesize a set of 4-methylumbelliferyl (MU) beta-1-->4-D-xylooligosides having the common structure [beta-D-Xyl-(1-->4)]2-5-beta-D-Xyl-MU. MU xylobioside synthesized chemically by the condensation of protected MU beta-D-xylopyranoside with ethyl 2,3,4-tri-O-acetyl-1-thio-beta-D-xylopyranoside was used as a substrate for transglycosylation with the beta-D-xylosidase from Aspergillus sp. to produce higher MU xylooligosides. The structures of oligosaccharides obtained were established by 1H and 13C NMR spectroscopy and electrospray tandem mass spectrometry. MU beta-D-xylooligosides synthesized were tested as fluorogenic substrates for the GH-10 family beta-D-xylanase from Aspergillus orizae and the GH-11 family beta-D-xylanase I from Trichoderma reesei. Both xylanases released the aglycone from MU xylobioside and the corresponding trioside. With substrates having d.p. 4 and 5, the enzymes manifested endolytic activities, splitting off MU, MUX, and MUX2 primarily.     

Kinetics of catalyzed hydrolysis of 4-methylumbelliferyl caprylate (MUCAP) salmonella reagent

The kinetics of chemical hydrolysis including neutral, acid- and base-catalyzed hydrolysis of 4-methylumbelliferyl caprylate (MUCAP) salmonella reagent were studied at different temperatures. The rate constants and activation parameters were determined by following the build-up of fluorescence peak of the hydrolysis product 4-methylumbelliferone (4-MU). The time scale of esterase enzyme hydrolysis caused by salmonella was compared with chemical hydrolysis as a background process.     

Use of polystyrene-supported DBU in the synthesis and alpha-selective glycosylation study of the unstable Schmidt donor of L-kedarosamine

In the alpha-glycosylation study of the unusual, 2-deoxy amino sugar of kedarcidin, polystyrene-supported DBU (PDBU) was found to be invaluable to the clean preparation of the highly labile Schmidt donor of l-kedarosamine. By further recognition that the C4-alcohol should be left free for favorable acceptor reactivity, we could for the first time successfully assemble the C13-O-alpha-glycoside of the ansamacrolide substructure of the kedarcidin chromophore. [reaction: see text]     

Synthesis of a non-natural T-antigen containing glycosphingolipid

A non natural glycosphingolipid containing the mucin derived, cancer associated disaccharide moiety Galbeta1-->3GalNAc, the T-antigen, alpha linked to a ceramide, has been synthesised via the protected disaccharide glycosyl trichloroacetimidate. The product has potential as a cancer vaccine.     

alpha-selective sialylations at -78 degrees C in nitrile solvents with a 1-adamantanyl thiosialoside

Novel 1-adamantanylthio sialosides were synthesized and coupled to acceptors under NIS/TfOH promotion conditions. These donors showed higher reactivity than the phenylthio sialosides and could be activated by NIS/TfOH in nitrile solvents at -78 degrees C to afford improved alpha-sialylations. With the N-acetyl-5-N,4-O-oxazolidinone-protected 1-adamantanylthio sialyl donor high alpha-selectivities could be achieved in the sialylations of both primary and sterically hindered secondary acceptors, including the important galactose 3-OH acceptors.     

Solid-phase synthesis of 4-biaryl-piperidine-4-carboxamides

A novel solid-phase synthesis of 4-biaryl-piperidine-4-carboxamides has been developed using FDMP resin with a carboxamide as the anchor point. With this approach, three points of diversity were incorporated into a GPCR-directed scaffold. Final products were obtained in good purity and yield.     

4-巯基-4-脱氧-4'-去甲表鬼臼毒素的立体控制合成

4-巯基-4-脱氧-4'-去甲表鬼臼毒素是合成4位硫取代的4'-去甲表鬼臼毒素的关键中间体,由4'-去甲表鬼臼毒素与硫化氢在BF~3·Et~2O存在下立体控制制备,也可通过以NH~3/CH~CN选择性 地水解4-乙酰硫基-4-脱氧-4'-去甲表鬼臼毒素而制备.     

Pre-activation based, highly alpha-selective O-sialylation with N-acetyl-5-N,4-O-carbonyl-protected p-tolyl thiosialoside donor

A new method for pre-activation of N-acetyl-5-N,4-O-carbonyl-protected p-tolyl thiosialoside donor with AgOTf and p-toluenesulfenyl chloride followed by coupling with other p-tolyl thioglycosides is reported. Excellent α-sialylation yields were achieved for these coupling reactions, as high as 91% yield of only α-isomer.     

Catalytic synthesis of 4-methylthiazol

The effect of the nature of individual oxides of Fe, Cr, Mo, Al, Si, disulfides of Mo, W and conditions of methylisopropylidenimine interaction with SO₂ on 4-methylthiazol formation have been studied. It is possible to accelerate the synthesis of 4-methylthiazol by Al and Si oxides having acid-base properties.     

Partial synthesis of 4'-demethylepipodophyllotoxin

4′-Demethylepipodophyllotoxin (III) has been synthesized by epimerisation of 4′-demethylpodophyllotoxin (I) via the corresponding chloride II. An improved method for the preparation of III has been developed by selective ether cleavage of the easily available podophyllotoxin (V) using the bromoderivatives VI and VII as intermediates.     

Chemoselectively template-assembled glycopeptide presenting clustered cancer related T-antigen

The first synthesis of the tumor-associated α-aminooxy T-antigen 1, a relevant recognition motif for the direct construction of multitopic carbohydrate architecture of biological interest is described. The usefulness of this building block is emphasized with the efficient preparation through oxime ligation of a neoglycopeptide cluster, which is readily suitable for evaluating the role of multivalency in antigen presentation to the immune system from an anticancer vaccine perspective.     

Practical synthesis of 2'-deoxy-4'-thioribonucleosides: substrates for the synthesis of 4'-thioDNA

We report herein a practical synthesis of 4'-thiothymidine (15) and appropriately protected 2'-deoxy-4'-thiocytidine (16), -thioadenosine (27), and -thioguanosine (29) derivatives, substrates for the synthesis of 4'-thioDNA, from the corresponding 4'-thioribonucleosides. 2'-deoxy-4'-thiopyrimidine nucleosides were synthesized using a radical reaction of the corresponding 2'-alpha-bromo derivatives, which were prepared via 2,2'-O-anhydro derivatives. 2'-deoxy-4'-thiopurine nucleosides were synthesized using the same radical reaction of the corresponding 2'-beta-bromo derivatives.     

The synthesis of 4-deazaformycin A

The preparation of 4-deazaformycin A has been achieved. The synthesis features the condensation of a suitably substituted, lithiated 4-picoline with 2,3,5-tri-O-benzyl-d-ribonolactone, dehydration of the resulting hemiacetal, and ionic hydrogenation, followed by manipulation of the protecting groups and subsequent ring closure with the formation of 7-amino-3-(beta-d-ribofuranosyl)pyrazolo[3,4-c]pyridine.     

A new synthesis of 4-thiouracils

Ethoxycarbonyl isothiocyanate has been found to form adducts with enamines which, on treatment with primary amines or ammonia, undergo apparent “amine exchange” and cyclization to 4-thiouracil derivatives. Evidence for the 4-thiouracil structure includes both spectral data and chemical transformations.