Facile selective detritylation of 5?-primary alcohols of pyrimidine nucleosides using tetra-n-butylammonium peroxydisulfate

Yang, Seungjoon; Lee, Dong Hoon; Kim, Yong Hae

doi:10.1002/(sici)1098-1071(1997)8:5<435::aid-hc8>3.0.co;2-7

Cited by 11 publications

(1 citation statement)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…13 To minimize depurination, at this stage we were convinced that DMT-deprotection must be executed under nonacidic or preferably neutral pH conditions. Among a variety of mild DMT removal conditions available in the literature, we evaluated ultrasound, 14 magnesium bromide, 15 tetra-n-butylammonium peroxydisulfate, 16 and sodium periodate 17 as options. This investigation led to the use of sodium periodate as a reagent of choice where complete detritylation was accomplished under mild conditions in an aqueous organic solvent.…”

Section: Route 2: Synthesis With Commercial Starting Materialmentioning

confidence: 99%

Development of a Kilogram-Scale Manufacturing Route for Bis-Tac-dG: Essential Building-Block for Guadecitabine

Wani,

Banerjee,

Davar

et al. 2024

Org. Process Res. Dev.

View full text Add to dashboard Cite

Guadecitabine (SGI-110) is a dinucleotide that is a prodrug of decitabine. The dinucleotide contains decitabine (top fragment) and 2′-deoxyguanosine (9; dG; bottom fragment) connected via a 3′ → 5′ phosphodiester bond. The manufacturing process of guadecitabine requires a large quantity of N 2 , 3′-O-(4-tert-butylphenoxyacetyl)-protected dG (2; Bis-Tac-dG) to incorporate the bottom fragment. The protected 2 being a critical starting material of the dinucleotide imposes stringent quality requirements for its synthesis and isolation. Presented herein is the development work leading to a practical and scalable route for compound 2 starting from commercial dG. Salient features of the approach included one-pot protection of 5′-OH group of N 2 -Tac-dG (3) with 4,4′-dimethoxytrityl (DMT) group followed by 3′-O-Tac protection furnishing fully protected dG 8, thus reducing the cycle time with fewer isolation steps and lowering the solvent usage. Subsequently, cleavage of DMT group from 8 utilizing NaIO 4 enabled a mild, highly selective, and robust route to produce high purity (>99%) Bis-Tac-dG on kilogram-scale. The structure and origin of major impurities were determined by comparison with reference standards and carefully controlled to an acceptable level in compound 2. The improved synthesis was scaled to prepare multiple ∼60 kg batches of 2 to supply all clinical studies up to phase III.

show abstract