2008
DOI: 10.1021/op800182x
|View full text |Cite
|
Sign up to set email alerts
|

Isolation, Synthesis, and Characterization of Impurities and Degradants from the Clofarabine Process

Abstract: The identification of clofarabine process impurities and their subsequent isolation, synthesis, and characterization is described. Two isomeric process impurities resulting from N 6 -attachment of a fluoroarabinose to clofarabine were found. Clofarabine's base degradation products, which were different from the process impurities, were also synthesized and characterized. These compounds resulted from modifications to the sugar moiety, the purine ring, or both. A mechanistic rationale for the formation of the

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1

Citation Types

0
6
0
3

Year Published

2010
2010
2023
2023

Publication Types

Select...
6
2

Relationship

0
8

Authors

Journals

citations
Cited by 14 publications
(9 citation statements)
references
References 7 publications
0
6
0
3
Order By: Relevance
“…Without going into details, it should be noted that a common drawback of both approaches is the indispensable introduction and subsequent removal of protective groups, which is associated with chromatographic purification in almost every step, a lack of selectivity of chemical reactions, and the problems associated with the poor regio-and stereoselectivity of chemical reactions (see, e.g. [12] and the papers cited therein).…”
Section: Introductionmentioning
confidence: 99%
“…Without going into details, it should be noted that a common drawback of both approaches is the indispensable introduction and subsequent removal of protective groups, which is associated with chromatographic purification in almost every step, a lack of selectivity of chemical reactions, and the problems associated with the poor regio-and stereoselectivity of chemical reactions (see, e.g. [12] and the papers cited therein).…”
Section: Introductionmentioning
confidence: 99%
“…Despite the detailed analysis and optimization of the clofarabine process [1213] and the bulk production of the protected nucleoside glycon 9 by chemists at Eli Lilly and Co. [18] this chemical synthesis is connected with the use of great volumes of organic solvents and gives rise to the formation of the undesired α-anomer necessitating the chromatographic purification of the desired β-anomer, and finally affords clofarabine in a low yield.…”
Section: Introductionmentioning
confidence: 99%
“…该路线一共 6 步反应, 总收率仅为 6%. 2004 年, ILEX 公 司 (San Antonio, TX, USA) 对 上 述 方 法 进 行 了 改 进 [7,8] (图 2, 路线 b). 他们采用单一 α-构型的 1-溴-2-脱 氧-2-β-氟-3,5-二-O-苯甲酰基-D-阿拉伯糖和 2,6-二氯嘌 呤缩合, 提高了反应的立体选择性(β/α=21/1), 经氨解 和脱保护基之后可得氯法拉滨.…”
unclassified