234436-48-7

Upstream product

• 239811-12-2 Benzoic acid (2R,3R,4R,5R)-2-(6-chloro-purin-9-yl)-4-hydroxy-5-trityloxymethyl-tetrahydro-furan-3-yl ester 
• 76-83-5 trityl chloride 
• 228243-48-9 6-chloro-9-(3-O-benzoyl-β-D-ribofuranosyl)purine 
• 98-88-4 benzoyl chloride 
• 144925-02-0 6-chloro-9-(5′-O-trityl-β-D-ribofuranosyl)purine 
• 2004-06-0 6-Chloropurine riboside 

Downstream Products

• 234436-49-8 9-[3-O-benzoyl-2-deoxy-2-fluoro-5-O-(triphenylmethyl)-β-D-arabinofuranosyl]-6-chloro-9H-purine 
• 234436-50-1 Benzoic acid (2R,3R,4R,5R)-5-(6-chloro-purin-9-yl)-4-(imidazole-1-sulfonyloxy)-2-trityloxymethyl-tetrahydro-furan-3-yl ester 
• 339196-22-4 5'-O-trityl-3'-O-benzoyl-2'-O-trifluoromethanesulfonyl-6-chloropurine riboside 
• 239811-12-2 Benzoic acid (2R,3R,4R,5R)-2-(6-chloro-purin-9-yl)-4-hydroxy-5-trityloxymethyl-tetrahydro-furan-3-yl ester 
• 110143-10-7 iodenosine 
• 234436-55-6 9-[2,3-dideoxy-2-fluoro-5-O-(triphenylmethyl)-β-D-threo-pentofuranosyl]-9H-purine-6-amine 
• 239811-11-1 9-(5-O-trityl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenine 
• 234436-54-5 9-(3-O-phenoxythiocarbonyl-5-O-trityl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenine 
• 265987-43-7 9-(5-O-trityl-3-O-methylthiothiocarbonyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl) adenine 
• 339196-23-5 thiocarbonic acid O-[5-(6-amino-purin-9-yl)-4-fluoro-2-trityloxymethyl-tetrahydro-furan-3-yl] ester O-(4-fluoro-phenyl) ester 
• 20187-82-0 9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenine 
• 1360874-39-0 9-(3-O-benzoyl-2-O-phenoxythiocarbonyl-5-O-trityl-β-D-ribofuranosyl)-6-chloropurine 
• 1360874-40-3 9-(3-O-benzoyl-5-O-trityl-β-D-2-deoxyribofuranosyl)-6-chloropurine 
• 1360874-41-4 [6-⁽¹⁵⁾N]-3'-O-benzoyl-5'-O-trityl-2'-deoxyadenosine 

Relevant academic research and scientific papers

INHIBITORS OF E1 ACTIVATING ENZYMES

This invention relates to compounds that inhibit El activating enzymes, pharmaceutical compositions comprising the compounds, and methods of using the compounds. The compounds are useful for treating disorders, particularly cell proliferation disorders, including cancers, inflammatory and neurodegenerative disorders; and inflammation associated with infection and cachexia.

An industrial process for synthesizing lodenosine (FddA)

Two industrial synthetic approaches to Lodenosine (1, FddA, 9-(2,3-dideoxy-2-fluoro-β-D-threo-pentofuranosyl) adenine) via a purine riboside or a purine 3′-deoxyriboside are described. Several novel applications of deoxygenation and fluorination methods are compared considering reaction yields, economy, safety and environmental concerns.

Improved synthesis of 9-(2,3-dideoxy-2-fluoro-β-D-threo-pentofuranosyl)adenine (FddA) using triethylamine trihydrofluoride

An improved synthesis of 9-(2,3-dideoxy-2-fluoro-β-D-threo-pentofuranosyl)adenine (1, FddA) via a fluorination of 3′-O-benzoyl-5′-O-tritylriboside (4a) using noncorrosive triethylamine trihydrofluoride (Et3N·3HF) is described. The method is suitable for large-scale synthesis. In particular, the synthesis of the pivotal intermediate 4a was much improved in avoidance of the use of toxic tin reagent. Radical deoxygenation with several silanes was also studied. The total yield of FddA from 6-chloropurine riboside (2) in this study was greater than that we reported previously.

PROCESS FOR PRODUCING NUCLEOSIDE DERIVATIVES

Nucleoside derivatives wherein the hydroxyl group at the 2'-position has been replaced by a fluorine atom, etc. and the hydroxyl group at the 3'-position has been deoxylated, such as 9-(2,3-dideoxy-2-fluoro-β-D-threo-pentofuranosyl) adenine (FddA), etc. and the compounds related thereto can be produced conveniently and at an advantage industrially from a purine riboside, by substituting a halogen atom for the 6-position in the purine riboside, modifying the hydroxyl groups at the 3'-and 5'-positions of the sugar moiety thereof with protecting groups which can not be deprotected (deblocked) under the same condition, further introducing a desired substituent group, such as a fluorine atom, etc. thereinto at the 2'-position of the sugar moiety and then deprotecting (deblocking)-deoxylating the protected hydroxyl group at the 3'-position thereof. Further, processes for producing important intermediates usable in the above production and thus produced novel intermediates are also provided.

Synthesis of 9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenine bearing a selectively removable protecting group

A facile and practical method to introduce fluorine at the up-side of the 2'-carbon of nucleosides is described. 6-Chloropurine riboside 3 was converted to the 3'-O-benzoate 4a via a stannylene complex, then converted to the 3'-O-benzoyl-5'-O-tritylriboside 5a. In the presence of pyridine, migration of the 3'-benzoyl groups of 4a and 5a to 2'-OH was rather slow. Hence, 5a was reacted with diethylaminosulfur trifluoride (DAST) in CH2Cl2 in the presence of pyridine to give the 2'-deoxy-2'-fluoroarabinoside 6 in good yield. The 3'-O-benzoyl-5'-O-trityl protecting system was easy to deprotect selectively. Thus, treatment of 6 with ammonia in MeOH gave the 5'- O-trityl compound 7, which was subjected to esterification with phenyl chlorothionoformate, radical deoxygenation with tris(trimethylsilyl)silane and acid treatment to afford 9-(2,3-dideoxy-2-fluoro-β-D-threo- pentofuranosyl)adenine (FddA) 2. In addition, acid treatment of 7 gave 9-(2- deoxy-2-fluoro-β-D-arabinofuranosyl)adenine (FdaraA) 1.