title: Process development for the synthesis of 5'-O-(4,4'-dimethoxytrityl)-N2-isobutyryl-2'-O-(2-methoxyethyl)-guanosine--a potential precursor for the second generation antisense oligonucleotides: an improved process for the preparation of 2'-O-alkyl-2,6-diaminopurine riboside.
abstract: An efficient four step process for the preparation of 5'-O-(4,4'-dimethoxytrityl)-N2-isobutyryl-2'-O-(2-methoxyethyl)-guanosine 1 was developed. Direct 2'-O-alkylation of 2,6-diaminopurine riboside 2 was accomplished via inexpensive and commercially available reagents such as KOH, DMSO and alkyl halides at room temperature in 4-6 hrs. Pure 2'-O-(2-methoxyethyl)-DAPR 3 was isolated by crystallization from methanol. Enzymatic deamination of 3 followed by selective N2-isobutyrylation and 5'-O-dimethoxytritylation furnished desired 1 in high yield and purity. Fully optimized four step synthetic process has been scaled up to the pilot plant level.
authors.affiliation: Shasun Chemicals and Drugs Limited, Chennai, India.
authors.forename: Shabbir Ali S
authors.initials: SA
authors.lastname: Taj
authors.forename: P
authors.initials: P
authors.lastname: Gurumurthy
authors.forename: R
authors.initials: R
authors.lastname: Suresh
authors.forename: S
authors.initials: S
authors.lastname: Narayanan
authors.forename: S
authors.initials: S
authors.lastname: Suman Meenakshi
authors.forename: Yogesh S
authors.initials: YS
authors.lastname: Sanghvi
mesh_terms: D006151:Guanosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D020320:Oligoribonucleotides, Antisense / Q000138:chemical synthesis*; D012263:Ribonucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D012266:Ribose / Q000031:analogs & derivatives*
chemical_list: D007202:Indicators and Reagents; D020320:Oligoribonucleotides, Antisense; D012263:Ribonucleosides; D006151:Guanosine; D012266:Ribose