- A mild and convenient approach for selective acetonide cleavage involved in carbohydrate synthesis using PPA-SiO2
-
Here, we report a highly selective, efficient and rapid method for the selective cleavage of primary acetonide using silica supported polyphosphoric acid (PPA-SiO2) for various carbohydrate substrates. Corresponding diols were obtained in good to excellent yields within 30 min using PPA-SiO2. Overall, PPA-SiO2 was found to be a useful catalyst for selective acetonide cleavage in carbohydrate substrates which may expand its utility in organic synthesis.
- Nikam, Rahul R.,Gore, Kiran R.
-
-
- NOVEL PROCESS FOR MAKING ALLOFURANOSE FROM GLUCOFURANOSE
-
The present invention relates to the manufacture of allofuranose from glucofuranose as defined in the description and in the claim. Allofuranos is an intermediate in the manufacture of oligonucleotides which can be used as a medicament.
- -
-
-
- FUCOSIDASE INHIBITORS
-
The present disclosure relates, in general, to compounds useful as inhibitors of fucosidase enzymes, and to methods and compositions for the treatment of tumors or cancers, such as liver disorders and liver tumors (e.g., hepatocellular carcinoma), with a compound as disclosed herein.
- -
-
-
- 6-Methylpurine derived sugar modified nucleosides: Synthesis and evaluation of their substrate activity with purine nucleoside phosphorylases
-
6-Methylpurine (MeP) is cytotoxic adenine analog that does not exhibit selectivity when administered systemically, and could be very useful in a gene therapy approach to cancer treatment involving Escherichia coli PNP. The prototype MeP releasing prodrug, 9-(β-d-ribofuranosyl)-6-methylpurine, MeP-dR has demonstrated good activity against tumors expressing E. coli PNP, but its antitumor activity is limited due to toxicity resulting from the generation of MeP from gut bacteria. Therefore, we have embarked on a medicinal chemistry program to identify non-toxic MeP prodrugs that could be used in conjunction with E. coli PNP. In this work, we report on the synthesis of 9-(6-deoxy-β-d-allofuranosyl)-6-methylpurine (3) and 9-(6-deoxy-5-C-methyl-β-d-ribo-hexofuranosyl)-6-methylpurine (4), and the evaluation of their substrate activity with several phosphorylases. The glycosyl donors; 1,2-di-O-acetyl-3,5-di-O-benzyl-α-d-allofuranose (10) and 1-O-acetyl-3-O-benzyl-2,5-di-O-benzoyl-6-deoxy-5-C-methyl-β-d-ribohexofuran-ose (15) were prepared from 1,2:5,6-di-O-isopropylidine-α-d-glucofuranose in 9 and 11 steps, respectively. Coupling of 10 and 15 with silylated 6-methylpurine under Vorbrüggen glycosylation conditions followed conventional deprotection of the hydroxyl groups furnished 5'-C-methylated-6-methylpurine nucleosides 3 and 4, respectively. Unlike 9-(6-deoxy-α-l-talo-furanosyl)-6-methylpurine, which showed good substrate activity with E. coli PNP mutant (M64V), the β-d-allo-furanosyl derivative 3 and the 5'-di-C-methyl derivative 4 were poor substrates for all tested glycosidic bond cleavage enzymes.
- Hassan, Abdalla E.A.,Abou-Elkhair, Reham A.I.,Parker, William B.,Allan, Paula W.,Secrist, John A.
-
-
- Anaerobic 5-Hydroxybenzimidazole Formation from Aminoimidazole Ribotide: An Unanticipated Intersection of Thiamin and Vitamin B12 Biosynthesis
-
Comparative genomics of the bacterial thiamin pyrimidine synthase (thiC) revealed a paralogue of thiC (bzaF) clustered with anaerobic vitamin B12 biosynthetic genes. Here we demonstrate that BzaF is a radical S-adenosylmethionine enzyme that catalyzes the remarkable conversion of aminoimidazole ribotide (AIR) to 5-hydroxybenzimidazole (5-HBI). We identify the origin of key product atoms and propose a reaction mechanism. These studies represent the first step in solving a long-standing problem in anaerobic vitamin B12 assembly and reveal an unanticipated intersection of thiamin and vitamin B12 biosynthesis.
- Mehta, Angad P.,Abdelwahed, Sameh H.,Fenwick, Michael K.,Hazra, Amrita B.,Taga, Michiko E.,Zhang, Yang,Ealick, Steven E.,Begley, Tadhg P.
-
p. 10444 - 10447
(2015/09/28)
-
- Synthesis of 2′-O,4′-C-alkylene-bridged ribonucleosides and their evaluation as inhibitors of HCV NS5B polymerase
-
The synthesis of 2′-O,4′-C-methylene-bridged bicyclic guanine ribonucleosides bearing 2′-C-methyl or 5′-C-methyl modifications is described. Key to the successful installation of the methyl functionality in both cases was the use of a one-pot oxidation-Grignard procedure to avoid formation of the respective unreactive hydrates prior to alkylation. The 2′-C-methyl- and 5′-C-methyl-modified bicyclic guanosines were evaluated, along with the known uracil-, cytosine-, adenine-, guanine-LNA and guanine-ENA nucleosides, as potential antiviral agents and found to be inactive in the hepatitis C virus (HCV) cell-based replicon assay. Examination of the corresponding nucleoside triphosphates, however, against the purified HCV NS5B polymerase indicated that LNA-G and 2′-C-methyl-LNA-G are potent inhibitors of both 1b wild type and S282T mutant enzymes in vitro. Activity was further demonstrated for the LNA-G-triphosphate against HCV NS5B polymerase genotypes 1a, 2a, 3a and 4a. A phosphorylation by-pass prodrug strategy may be required to promote anti-HCV activity in the replicon assay.
- Chapron, Christopher,Glen, Rebecca,La Colla, Massimiliano,Mayes, Benjamin A.,McCarville, Joseph F.,Moore, Stephen,Moussa, Adel,Sarkar, Ruhul,Seifer, Maria,Serra, Ilaria,Stewart, Alistair
-
p. 2699 - 2702
(2014/06/09)
-
- Environment friendly chemoselective deprotection of acetonides and cleavage of acetals and ketals in aqueous medium without using any catalyst or organic solvent
-
Highly chemoselective environment friendly deprotection of acetonides and cleavage of acetals and ketones has been achieved by heating in aqueous medium without using any catalyst and organic solvent. Indian Academy of Sciences.
- Mukherjee,Sengupta,Roy
-
p. 1493 - 1496
(2014/04/03)
-
- N-Thiocarbonyl iminosugars: Synthesis and evaluation of castanospermine analogues bearing oxazole-2(3H)-thione moieties
-
A straightforward and efficient synthetic route to a new class of glycosidase inhibitors containing an oxazole-2(3H)-thione moiety has been devised. The approach involves the formation of α-hydroxy ketones, which, after condensation with thiocyanic acid, leads to the formation of the heterocycle. By exploiting the ability of the nitrogen atom of oxazoline-2-thione precursors to act as nucleophiles in intramolecular addition, castanospermine analogues could be readily prepared in good overall yields. Glycosidase inhibitory activity compared to oxazolidinethione analogues showed a strong influence of the double bond, for example with pseudoiminosugar 19, by suppressing α-glucosidase inhibition and introducing, to a moderate level, β-glucosidase inhibitory activity. Reactivities showed the propensity of oxazole-2(3H)-thiones - especially when fused on carbohydrate frames - to convert into 1,3-oxazolidine-2-thione aminals through nucleophilic addition to the double bond, leading to unexpected tricyclic structure 21. Oxazole-2(3H)-thione moieties have been anchored onto carbohydrates in a five-step sequence that allows access to castanospermine analogues. Copyright
- Silva, Sandrina,Sanchez-Fernandez, Elena M.,Ortiz Mellet, Carmen,Tatibouet, Arnaud,Pilar Rauter, Amelia,Rollin, Patrick
-
p. 7941 - 7951
(2014/01/06)
-
- Useful methods for the synthesis of isopropylidenes and their chemoselective cleavage
-
A catalytic amount of phosphotungstic acid (PTA) has been found to be a very effective catalyst for isopropylidenation of 1,2-diols and their deprotection at room temperature. The ease of handling, cost and activity of the catalyst, good to excellent yields and chemoselectivity for deprotection are some of the highlights of the reported method.
- Vanlaldinpuia, Khiangte,Bez, Ghanashyam
-
supporting information; experimental part
p. 3759 - 3764
(2011/08/06)
-
- Synthesis of fused cyclic systems containing medium-sized rings through tandem ROM-RCM of norbornene derivatives embedded in a carbohydrate template
-
A general approach for the synthesis of fused cyclic systems containing medium-sized rings (7-9) has been developed. The key steps involve a diastereoface-selective Diels-Alder reaction of the dienophiles 4a-d attached to a furanosugar with cyclopentadiene and ring opening (ROM)-ring closing metathesis (RCM) of the resulting norbornene derivatives 10a-d and 11a-d. Diels-Alder reaction of the dienophiles 4a-d with cyclopentadiene in the absence of a catalyst produced 10a-d as the major product arising through addition of the diene to the unhindered Si-face. The most interesting and new aspect of the Diels-Alder reaction of these dienophiles is the accessibility of the Re-face that was blocked by the alkenyl chains under Lewis acid catalysis producing the diastereoisomers 11a-d exclusively. The reversal of facial selectivity from an uncatalyzed reaction to a catalyzed one is unprecedented. The observed stereochemical dichotomy is attributed to rotation of the enone moiety along the o bond linking the sugar moiety during formation of the chelate 13. This makes the Re-face of the enone moiety in 4a-d unhindered. Diels-Alder reaction of the carbocyelic analogue 15 under Lewis acid catalysis produced a 1:1 mixture of the adducts 16 and 17 confirming the participation of sugar ring oxygen in chelate formation. Finally ROM-RCM of 10a-d and 11a-d with Grubbs' catalyst afforded the cis-syn-cis and cis-anti-cis bicyclo-annulated sugars 21a-d and 23a-d, respectively, containing 7-9 membered rings.
- Malik, Chanchal K.,Yadav, Ram Naresh,Drew, Michael G. B.,Ghosh, Subrata
-
supporting information; experimental part
p. 1957 - 1963
(2009/08/07)
-
- Mechanistic studies on pyridoxal phosphate synthase: The reaction pathway leading to a chromophoric intermediate
-
Two routes for the de novo biosynthesis of pyridoxal-5′-phosphate (PLP) have been discovered and reconstituted in vitro. The most common pathway that organisms use is dependent upon the activity of just two enzymes, known as Pdx1 (YaaD) and Pdx2 (YaaE) in
- Hanes, Jeremiah W.,Burns, Kristin E.,Hilmey, David G.,Chatterjee, Abhishek,Dorrestein, Pieter C.,Begley, Tadhg P.
-
p. 3043 - 3052
(2008/09/19)
-
- Synthesis of 5-Azacytidine nucleosides with rigid sugar moiety as potential antitumor agents
-
The bicyclic 3′-O,5′-C-methylene-linked and 2′-O,5′-C-methylene-linked 5-azacytidine derivatives were readily synthesized from 1,2;5,6-di-O-isopropylidene-D-glucose and evaluated against several cancer cell lines.
- Chun, Moon Woo,Kim, Myong Jung,Kim, Hea Ok,Kim, Hee-Doo,Kim, Joong Hyup,Moon, Hyung Ryong,Jeong, Lak Shin
-
p. 915 - 917
(2007/10/03)
-
- Conformationally constrained analogues of diacylglycerol (DAG). Part 19: Asymmetric syntheses of (3R)- and (3S)-3-hydroxy-4,4-disubstituted heptono-1,4-lactones as protein kinase C (PK-C) ligands with increased hydrophilicity
-
The stereospecific introduction of (R)- and (S)-OH groups at position C-3 of two diacylglycerol γ-lactones (DAG-lactones) previously identified as strong protein kinase C (PK-C) ligands is presented. The compounds were designed to investigate whether the extra OH group in a specific orientation could establish an additional hydrogen bond with the C1 domain of PK-C, thus providing a DAG analogue with reduced lipophilicity. The OH groups were introduced following two different diastereoselective multistep syntheses starting from diacetone-D-glucose. The PK-C binding affinities for the new compounds were weaker in comparison to those of the parent compounds, suggesting that the extra OH does not engage efficiently in hydrogen bonding at the receptor.
- Nacro, Kassoum,Lee, Jeewoo,Barchi Jr., Joseph J,Lewin, Nancy E,Blumberg, Peter M,Marquez, Victor E
-
p. 5335 - 5345
(2007/10/03)
-
- Amide-Modified Oligonucleotides with Preorganized Backbone and Furanose Rings: Highly Increased Thermodynamic Stability of the Duplexes Formed with their RNA and DNA Complements
-
The amide backbone modification C3′-CH2-CONH-C5′ has been further modified by introducing a methyl at C5′, either in R or in S configuration. Only the S stereoisomer can adopt the required geometry to fit into a duplex with complementary RNA. A
- De Mesmaeker, Alain,Lebreton, Jacques,Jouanno, Chantal,Fritsch, Valérie,Wolf, Romain M.,Wendeborn, Sebastian
-
p. 1287 - 1290
(2007/10/03)
-
- Halichondrins and related compounds
-
Novel chemical compounds that can be used to synthesize halichondrin B and norhalichondrin B, and related derivatives. The total synthesis of halichondrin B and norhalichondrin B is also disclosed.
- -
-
-
- Synthesis of 5'-deoxy-5'-difluoromethyl phosphonate nucleotide analogs
-
A synthetic route to nucleoside 5'-deoxy-5'-difluoromethyl phosphonates from ribofuranosyl 5-deoxy-5-difluoromethyl phosphonate precursors is described. Methyl 5,6-dideoxy-6-(diethoxyphosphinyl)-6,6-difluoro-2,3-O- isopropylidene-β-D-ribo-hexofuranoside (7) was converted, under mild conditions, to the suitable glycosylating agent 1-O-acetyl-2,3-di-O-benzoyl-5,6-dideoxy-6-(diethoxyphosphinyl) -6,6-dif luoro-β-D-ribo-hexofuranoside (10). 1,2-Di-O-acetyl-3-O-benzyl-5,6-dideoxy-6-(diethoxyphosphinyl)- 6,6-difl uoro-β-D-ribo-hexofuranoside (16) was also prepared as a versatile building block for nucleotide synthesis. Condensation of 10 with silylated nucleobases, followed by complete deprotection, afforded 5',6'-dideoxy-6'-(dihydroxyphosphinyl)-6',6'-difluoro nucleoside analogs 22a-c. In the case of the glycosylation of adenine, a considerable quantity of N-7 regioisomer 19 was formed. 5',6'-Dideoxy-6'-(dihydroxyphosphinyl)-6',6'-difluoro adenosine analog 22c was converted into the triphosphate analog 23 using 1,1'-carbonyldiimidazole activation followed by condensation with pyrophosphate. The adenosine 3',5'-cyclic monophosphate analog 24 was obtained through the DCC promoted intramolecular cyclization of 22c. Dinucleoside phosphate analog 27 was prepared by DCC-catalyzed coupling of 1-[2,3-di-O-benzoyl-5,6-dideoxy-6-(dihydroxyphosphinyl)-6,6- di fluoro-β-D-ribo-hexofuranosyl]uracil (21a) with 2',5'-bis(O-tert-butyldimethylsilyl)-N4-acetyl-cytidine (25), followed by deprotection.
- Matulic-Adamic,Haeberli,Usman
-
p. 2563 - 2569
(2007/10/02)
-
- The use of free radical cyclization in the synthesis of compounds related to the mannostatins
-
A study of the potential use of 5-exo free radical cyclizations in the synthesis of carbocyclic compounds related to the mannostatins 1 and 2 is described. The dithioacetal 8 was prepared and the methyl oxime moiety utilised as an intramolecular radical t
- Ingall,Moore,Roberts
-
p. 2155 - 2162
(2007/10/02)
-
- SYNTHESIS OF TWO RIGID DIACYLGLYCEROL ANALOGUES HAVING A PERHYDRO FUROFURAN BIS-γ-BUTYROLACTONE SKELETON. 3.
-
The stereoselective synthesis of two new bis-γ-butyrolactones starting from 1,2:5,6-di-O-isopropylidene-α-D-allofuranose was completed in 22 steps.One of the isomers (3a) showed very good binding affinity towards protein kinase C.
- Lee, Jeewoo,Marquez, Victor E.,Bahador, Afshin,Kazanietz, Marcelo G.,Blumberg, Peter M.
-
p. 4317 - 4320
(2007/10/02)
-
- Radical Cyclisation Reactions Leading to Polyhydroxylated Cyclopentane Derivatives: Synthesis of (1R,2R,3S,4R)- and (1S,2S,3R,4S)-4-Hydroxyethylcyclopentane-1,2,3-triol
-
The tetrol (-)-1 has been prepared from a derivative of (D)-allose 3.The stereoselective carbocyclization reaction (8->11) formed the key step in this sequence.The enantiomeric cyclopentane derivative (+)-1 was also prepared from compound 3.In this synthe
- Roberts, Stanley M.,Shoberu, Karoline A.
-
p. 2625 - 2632
(2007/10/02)
-
- N-ACYLAMINO ACID DERIVATIVES AND THEIR PHARMACEUTICAL COMPOSITIONS
-
An N-acylamino acid derivative of the formula: STR1 wherein the substituents are herein defined or a salt thereof, which is useful as hypotensive drugs.
- -
-
-
- Method of inhibiting virus
-
A group of five- and six-membered heterocyclic compounds having a nitrogen in the ring and 2 to 3 hydroxyl substituents on the ring are effective inhibitory agents of human immunodeficiency virus.
- -
-
-