轮环藤宁：从实验室到生命 Cyclen:From Laboratory to Life

Synthesis of Cyclen

Since the 1960s, extensive research has been conducted on polyaza macrocyclic compounds. Among them, Cyclen (1,4,7,10-tetraazacyclododecane) and its derivatives have garnered considerable attention owing to their robust coordination capabilities with metal ions. Various methodologies exist for synthesizing Cyclen, including the Stetter synthesis, Richman-Atkins synthesis, Weisman synthesis, glyoxal condensation, and diethyl oxalate synthesis. In industrial production, the classic and high-yielding Richman-Atkins synthesis method is predominantly employed. This method utilizes diethylenetriamine and diethanolamine, proceeding through p-toluenesulfonylation, ring closure, deprotection, salt formation, alkalization, and finally isolation.

Properties of Cyclen

The Cyclen molecule possesses four imino groups, offering diverse opportunities for the preparation of various N-substituted derivatives. The four nitrogen atoms within the Cyclen ring are capable of forming stable complexes with metal ions, leading to their extensive utilization in various domains such as medicine, the development of enzyme mimics, metal cation extraction, and other advanced applications.

Applications of Cyclen

· Pharmaceutical field

One of the pivotal applications of Cyclen derivatives lies in the synthesis of various contrast agents that are indispensable for medical imaging. A notable example is Na[Gd(DOTA)(H2O)], where DOTA, a derivative of Cyclen, serves as a crucial component in MRI contrast agents.

· Catalysis and Molecular Recognition

Cyclen and its metal complexes have a wide range of uses in catalysis, molecular recognition, and as fluorescent probes, among other applications. By chemically modifying Cyclen, its functionality can be significantly enhanced, opening up further opportunities for scientific research and industrial applications.

· Solar Cells

Recent studies indicate that Cyclen molecules can enhance the performance of perovskite solar cells. Through the control of high-quality film production, Cyclen is able to diminish non-radiative recombination and prolong carrier lifetime, which in turn boosts the efficiency of the solar cells.

Cyclen Related Intermediates

Cyclen intermediates continue to captivate researchers due to their potent chelating capabilities for metal ions, resulting in complexes with a range of unique functions. Cyclen has applications in medicine, enzyme imitation, separation processes, and carrier gases, as well as in the extraction of metal cations. When Cyclen is appropriately modified, it can significantly enhance its coordination properties and the functionality of its complexes, making it a selective ligand for transition metals, heavy metals, lanthanides, and actinides in biomedical applications. Cyclen N, when attached to side chain groups like esters, amides, or pyridines, can act as a ligand for alkali metal cations, enabling the high-selectivity extraction of metal ions. Furthermore, Cyclen and its derivatives are instrumental in developing contrast agents and radioactive imaging agents for magnetic resonance imaging diagnostics in medicine, and their heavy metal complexes serve as X-ray contrast agents. Following crown ethers and cryptands, Cyclen and its derivatives represent another class of functional ligands with distinctive coordination characteristics. Their structural resemblance to chlorophyll, heme, and numerous biological enzymes allows their use in chemical simulation, molecular recognition, molecular magnets, and catalysts for biological and chemical reactions.

Chemically Inspired Dreams

Accelerate Drug Discovery

上海凌凯科技股份有限公司

LinkChem Technology Co., Ltd.

— 上海总部研发中心 — 

凌凯科技·LinkChem成立于2011年，是一家专注于有机合成化学、流体工程技术应用的研发型产业化高新技术企业，主要提供小分子化合物研发、生产及商业化解决方案。公司业务横跨且深耕医药、新材料、新能源三大领域，以创新驱动、工程工艺协同，实现对客户多元化需求的快速响应、加速产品服务落地、帮助客户提升整体经济效益。

历经13年发展，凌凯科技有着深厚的研发实力和产业转化能力。公司拥有超8,600㎡研发运营中心，依托经验丰富、实力强劲的核心研发团队，搭建一站式生物医药 CDMO平台；坚持实施科技创新驱动战略，自主研发 “流动化学与微通道”、“绿色催化”两大核心技术平台，推进工艺创新与产业升级；公司旗下两座商业化生产工厂，建造了业内一流车间，聚力发展新质生产力，实现生产规模化、智能化与高效化。
通过持续和深入的商业化布局，公司业务已覆盖全球五大洲，与5,000多家制药企业和研发机构建立了良好合作关系。凌凯科技始终以市场需求为导向，秉承“科学、严谨、创新、合作”的发展理念，立足中国，辐射全球，致力于成为全球客户值得信赖的医药、新材料与新能源领域重要合作伙伴，不断为生命健康和绿色能源革新事业贡献力量。

上海凌富药物研究有限公司

Linkfull Laboratories Co., Ltd.

— 原料药研发及生产 —

上海凌凯科技旗下的控股子公司：上海凌富药物研究有限公司，是由上海凌凯科技股份有限公司与江西富祥药业股份有限公司联合发起并成立。新成立的合资公司凭借上海凌凯科技多年来积累的丰富研发经验和市场终端客户资源，以及江西富祥药业国际质量监管理念接轨的GMP管理体系、科学完善的EHS管理体系，进一步深耕CDMO全球国际业务。合资公司凭借上海的地域优势、信息优势和人才优势，积极扩充研发人员，建设专业人才队伍，提高企业的研发创新服务能力，稳步推进创新药从临床前研究到商业化生产的一体化综合服务能力，增强企业的整体竞争力。

上海旭流化学科技有限公司

Shanghai XFlow Chemical Technology Co., Ltd.

上海旭流化学科技有限公司是一家专业做新催化剂应用研究和流动化学技术开发的公司。公司位于上海市浦东新区康新公路3399号5号楼，在上海拥有1600平方米的研发实验室，拥有员工35名，实验室内拥有CSTR、PFR、微通道反应器、连续空气氧化反应器、连续格式反应器、固定床、滴流床反应器，连续光反应器等等各种流动化学的反应器装置。在江西的5000平方米的中试车间也正在建设之中。公司有工艺开发/反应器设计/工艺模拟/工程设计/工艺安全/分析支持等部门。

公司在反应的连续化工艺开发中有一定的经验，并已实施了多个产品的多步连续工艺，帮助客户实现了传统间歇反应釜工艺向连续流技术的升级和改造，也帮助客户开发出新催化剂的工艺，取得了非常好的社会效应和经济效应。

江西亚太科技发展有限公司

Jiangxi Yatai Technology Co., Ltd. 

— 中试研究与商业化生产 —

2018年下半年，上海凌凯科技全资收购江西亚太科技，一家高端医药中间体生产工厂。目前江西亚太工厂一、二期改造均已完成，工厂采用国际先进的EHS管理体系，目前已完全具备完善的研发，中控与商业化生产能力。江西亚太科技已于2020年通过跨国知名制药集团如AMGEN,SANOFI等全球知名药企的现场审计。2021年上半年，江西亚太科技自主新建的7000平米研发中心完成装修并全面投入使用，该研发中心集研发、中试、分析和行政办公于一体，并配备高端的连续流技术专用实验室，可同时容纳60-80个新药分子砌块项目的试验开展工作。

江西凌富生物科技有限公司

Jiangxi Linkfull Biological Technology Co., Ltd.

— 高级中间体和原料药（GMP） —

江西凌富生物科技有限公司是上海凌富药物研究有限公司在景德镇设立的全资子公司，当年新征化工用地700亩，一期300亩已经投入建设及手续合法化进程中。

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