合成抗肿瘤药物 (2R,3R,4S,5R)-5-(6-氨基-2-氯嘌呤-9-基)-4-氟-2-(羟甲基)氧杂戊环-3-醇(氯法拉滨)的简单高效途径

IF 0.7 4区 化学 Q4 CHEMISTRY, ORGANIC Letters in Organic Chemistry Pub Date : 2024-02-22 DOI:10.2174/0115701786287468240209105224
Laxmi Kumari Nagarapu, Chithaluri Sudhakar, Suresh Babu Namani
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引用次数: 0

摘要

:氯法拉滨(1)是一种用于治疗急性白血病的抗癌剂。这项工作揭示了开发一种方便、环保、高产的氯法拉滨(1)合成方案的努力。合成过程包括对 2-脱氧-2-β-氟-1,3,5-三-O-苯甲酰基-1-α-D-呋喃核糖(6)进行溴化,然后与 2,6-二氯嘌呤(4)进行 C-N 偶联,并连续进行选择性胺化。拟议的总合成包括五个步骤,总收率为 65-70%,纯度为 99.85%。本工艺采用简单的纯化过程制备氯法拉滨 (1),反应时间短,收率高,纯度高,且不使用有毒和发火化学品。
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A Simple and Efficient Path for the Synthesis Antineoplastic Agent (2R,3R,4S,5R)-5-(6-Amino-2-Chloropurin-9-yl)-4-Fluoro-2-(Hydroxymethyl) oxolan-3-ol (Clofarabine)
: Clofarabine (1) is an anticancer agent used to treat acute leukemia. This work discloses the efforts to develop a convenient, environmentally benign, and high-yielding synthetic protocol leading to Clofarabine (1). The synthesis includes bromination of 2-deoxy-2-β-fluoro-1,3,5-tri-O-benzoyl-1- α-D-ribofuranose (6), followed by C-N coupling with a 2,6-dichloro purine (4) and selective amination consecutively. The proposed total synthesis comprises five steps to afford an overall yield of 65- 70% with 99.85% purity. The present process provides preparation of Clofarabine (1) using a simple purification process with lesser reaction time, better yield, and purity without using toxic and pyrophoric chemicals.
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来源期刊
Letters in Organic Chemistry
Letters in Organic Chemistry 化学-有机化学
CiteScore
1.30
自引率
12.50%
发文量
135
审稿时长
7 months
期刊介绍: Aims & Scope Letters in Organic Chemistry publishes original letters (short articles), research articles, mini-reviews and thematic issues based on mini-reviews and short articles, in all areas of organic chemistry including synthesis, bioorganic, medicinal, natural products, organometallic, supramolecular, molecular recognition and physical organic chemistry. The emphasis is to publish quality papers rapidly by taking full advantage of latest technology for both submission and review of the manuscripts. The journal is an essential reading for all organic chemists belonging to both academia and industry.
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