84709-46-6

Upstream product

• 30725-00-9 2,3-O-isopropylidene-D-ribonic-γ-lactone 
• 3969-84-4 3,4-di-O-isopropylidene-D-mannitol 
• 76-83-5 trityl chloride 
• 84608-23-1 3,4-O-isopropylidene-1-O-trityl-D-mannitol 
• 113626-56-5 (2S,3S,4S)-2,3-dihydroxy-4-trityloxymethyl-4-butanolide 
• 101758-68-3 (R)-(+)-5-triphenylmethyloxymethyl-2 (5H)-furanone 
• 5336-08-3 D-Ribono-1,4-lactone 
• 532-20-7 D-Ribose 
• 106886-17-3 2,3-O-isopropylidene-5-O-triphenylmethyl-D-ribono-1,4-lactone 
• 113571-56-5 (2S,3S,4S)-2,3-isopropylidenedioxy-4-trityloxymethyl-4-butanolide 
• 54503-64-9 2,3-O-isopropylidene-5-O-trityl-D-ribofuranose 
• 55726-19-7 2,3-O-Isopropylidene-5-O-trityl-D-ribofuranose 

Downstream Products

• 88559-47-1 2,2-Dimethyl-propionic acid (4S,5R)-5-((R)-1-hydroxy-2-trityloxy-ethyl)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl ester 
• 141410-49-3 (2S,3R,4S)-1-benzyl-2-(hydroxymethyl)pyrrolidine-3,4-diol 
• 69434-51-1 1-(Adenin-9-yl)-1-deoxy-D-arabitol 
• 84608-25-3 Toluene-4-sulfonic acid (4R,5R)-5-((R)-1-hydroxy-2-trityloxy-ethyl)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl ester 
• 163226-43-5 1-O-tert-butyldimethysilyl-2,3-O-isopropylidene-5-O-tritylribitol-4-ulose 

Relevant academic research and scientific papers

Synthesis of Terminal Ribose Analogues of Adenosine 5′-Diphosphate Ribose as Probes for the Transient Receptor Potential Cation Channel TRPM2

TRPM2 (transient receptor potential cation channel, subfamily M, member 2) is a nonselective cation channel involved in the response to oxidative stress and in inflammation. Its role in autoimmune and neurodegenerative diseases makes it an attractive pharmacological target. Binding of the nucleotide adenosine 5′-diphosphate ribose (ADPR) to the cytosolic NUDT9 homology (NUDT9H) domain activates the channel. A detailed understanding of how ADPR interacts with the TRPM2 ligand binding domain is lacking, hampering the rational design of modulators, but the terminal ribose of ADPR is known to be essential for activation. To study its role in more detail, we designed synthetic routes to novel analogues of ADPR and 2′-deoxy-ADPR that were modified only by removal of a single hydroxyl group from the terminal ribose. The ADPR analogues were obtained by coupling nucleoside phosphorimidazolides to deoxysugar phosphates. The corresponding C2″-based analogues proved to be unstable. The C1″- and C3″-ADPR analogues were evaluated electrophysiologically by patch-clamp in TRPM2-expressing HEK293 cells. In addition, a compound with all hydroxyl groups of the terminal ribose blocked as its 1″-β-O-methyl-2″,3″-O-isopropylidene derivative was evaluated. Removal of either C1″ or C3″ hydroxyl groups from ADPR resulted in loss of agonist activity. Both these modifications and blocking all three hydroxyl groups resulted in TRPM2 antagonists. Our results demonstrate the critical role of these hydroxyl groups in channel activation.

N-Benzyl Substitution of Polyhydroxypyrrolidines: The Way to Selective Inhibitors of Golgi α-Mannosidase II

Inhibition of the biosynthesis of complex N-glycans in the Golgi apparatus influences progress of tumor growth and metastasis. Golgi α-mannosidase II (GMII) has become a therapeutic target for drugs with anticancer activities. One critical task for successful application of GMII drugs in medical treatments is to decrease their unwanted co-inhibition of lysosomal α-mannosidase (LMan), a weakness of all known potent GMII inhibitors. A series of novel N-substituted polyhydroxypyrrolidines was synthesized and tested with modeled GH38 α-mannosidases from Drosophila melanogaster (GMIIb and LManII). The most potent structures inhibited GMIIb (Ki=50–76 μm, as determined by enzyme assays) with a significant selectivity index of IC50(LManII)/IC50(GMIIb) >100. These compounds also showed inhibitory activities in in vitro assays with cancer cell lines (leukemia, IC50=92–200 μm) and low cytotoxic activities in normal fibroblast cell lines (IC50>200 μm). In addition, they did not show any significant inhibitory activity toward GH47 Aspergillus saitoiα1,2-mannosidase. An appropriate stereo configuration of hydroxymethyl and benzyl functional groups on the pyrrolidine ring of the inhibitor may lead to an inhibitor with the required selectivity for the active site of a target α-mannosidase.

Syntheses of cyclopentyl nucleoside (?)-neplanocin A through tetrazole-fragmentation from cyanophosphates

We recently reported a novel synthetic method for five-membered unsaturated cyclic compounds from ketones involving cyanophosphates (CPs) under neutral conditions, in which alkylidene carbenes generated through tetrazole-fragmentation undergo [1,5]-C–H in

S-Ribosylhomocysteine analogues modified at the ribosyl C-4 position

4-C-Alkyl/aryl-S-ribosylhomocysteine (SRH) analogues were prepared by coupling of homocysteine with 4-substituted ribofuranose derivatives. The diastereoselective incorporation of the methyl substituent into the 4 position of the ribose ring was accomplis

Synthesis of enantiomerically pure 4-substituted riboses

An efficient and flexible synthesis of 4-substituted ribose analogues is described. The key step involves the simple addition of a Grignard reagent to a ketone derived from a commercially available ribose. The addition of a range of Grignard reagents proc

Synthesis of peracylated derivatives of L-ribofuranose from D-ribose and their use for the preparation of β-L-ribonucleosides

A practical synthesis of peracylated derivatives of β-L-ribofuranose 13-15 from D-ribose was accomplished in 6 steps (total yield: 30-45percent). Compound 13 was employed for the preparation of 1-(β-L-ribofuranosyl)thymine (16) and -cytosine (17), which are key intermediates for the preparation of the nucleoside derivatives with β-L-configuration. Simultaneous transformation of 17 into β-L-ddC (19) and β-L-3′dC (20) was studied.

A new route to some enantiomerically pure substituted morpholines from D-ribono- and D-gulono-1,4-lactones

D-Ribono-1,4-lactone, after acetalation, tritylation, and reduction, leads to a cyclization compound which gave with tosyl chloride 1,4-anhydro-2,3-O-isopropylidene-5-O-trityl-D-ribitol.The latter was transformed (acid hydrolysis, periodate oxidation, reduction, tritylation, and tosylation) into a ditosylated derivative 16, which was cyclized into morpholines by the action of primary amines.Acid hydrolysis, followed by acetylation, gives the (2S)-acetoxymethyl-4-isopropyltetrahydro-1,4-oxazine (21).A similar sequence has been applied to D-gulonolactone to give access to oxazines 33, 34, and 35. Keywords: Synthesis; D-Ribono-1,4-lactone; D-Gulono-1,4-lactone; Morpholine derivatives

Hydroxylated pyrrolidines. Synthesis of 1,4-dideoxy-1,4-imino-L-lyxitol, 1,4,5-trideoxy-1,4-imino-D- and -L-lyxo-hexitol, 2,3,6-trideoxy-3,6-imino-D-glycero-L-altro- and -D-glycero-L-galacto-octitols, and of a chiral potential precursor of carbapenem systems

Enantiospecific syntheses are reported for the title pyrrolidines, from carbohydrate precursors. An intermediate in one of the routes, ethyl 2,3,6-trideoxy-3,6-imino-4,5:7,8-di-O-isopropylidene-D-glycero-L-altro-octonate (23), could be converted in two steps into a β-lactam.

A synthetic approach towards neplanocin A: Preparation of the optically active cyclopentene moiety from D-ribose

D (-)-ribose has been converted to the chiral 2-cyclopenten-1-one derivative 13 which has the correct stereochemistry and appropriate functionalities for the construction of neplanocin A.