Synthesis of Novel Nitrogen Mustards Containing Amino Alcohol Derivatives Aïcha. Amira, Malika. Berredjem, and Nour-Eddine. Aouf Laboratory of Applied Organic Chemistry (LAOC), Bioorganic Chemistry Group, Chemistry Department, Sciences Faculty, Badji-Mokhtar-Annaba University, Box 12, 23000 Annaba, Algeria Email: minaamira75@yahoo.fr, {malika.berredjem, noureddine.aouf}@univ-annaba.dz Abstract—Nitrogen mustards are an extremely active class of alkylating agents that have widespread clinical application in the treatment of various tumors. A Novel series of 1,1-bis(2-chloroethyl)-3-(2-hydroxy ethyl)urea 3(a-c) having different substituent on C-2 have been synthesized from a number of simple and chiral amino alcohols derivatives prepared by reduction of amino acids. Nitrogen mustard motif is introduced by acylation of bis (2- chloroethyl) amine with ethyl chloroform ate in water. The aminolysis of ethyl ester with a variety of amino alcohols in solvent-free conditions is the key step to give the desired products. All structures of the compounds were analyzed by different spectroscopic methods. Index Terms—nitrogen mustard, acylation, amino alcohol, aminolysis I. INTRODUCTION Cancer is major health hazard for the world surpassing heart diseases. Each year, tens of millions of people are diagnosed with cancer around the world, and more than half of the patients eventually die from it. Surgery, radiotherapy, and chemotherapy are the most common types of cancer treatment. The last category include several class based on their biochemical structure and mechanism of action. Alkylating agents are the oldest group of chemotherapeutics in use today, and nitrogen mustards are an important subtype of this class widely used in the treatment of a variety of cancer. [1] Figure 1. Nitrogen mustards agents. Manuscript received March 1, 2015; revised August 25, 2015. Chlorethamine [2], Cyclophosphamide [3] and Chlorambucil [4] (Fig. 1) are the most potent and effective drugs react as bifunctional alkylating agents. N,N-bis(2-chloroethyl)amine pharmacophore, is believed to exert the antitumoral activity through interstrand cross-linking in the major groove of DNA and this linkage represents the highest toxicity of all alkylation events [5]-[7]. Development of resistance against the existing anticancer drugs keeps research window open in search of newer anticancer molecules. Here we report an attempt to achieve new potent antitumor agents by the synthesis, characterization of novel nitrogen mustards containing amino alcohols derivatives. Many bioactive natural products and medical molecules consist of amino alcohols structural motifs due to their importance in asymmetric synthesis [8], peptide and pharmaceutical chemistry [9], resolution of racemic mixtures [10], synthesis of insecticidal compounds [11], and others. Figure. 2. Synthesis of nitrogen mustards containing amino alcohols derivatives The direct transformation of ester to amide is a potentially important step in this route, the amide bond is among the most common chemical function present in natural or synthetic organic molecules, is generally carried out under harsh conditions requiring high temperatures and extended reaction times [12]. An Journal of Life Sciences and Technologies Vol. 3, No. 2, December 2015 65 © 2015 Journal of Life Sciences and Technologies doi: 10.18178/jolst.3.2.65-68