Marise Garcia Batlle
National Autonumous University of Mexico, Mexico
Title: Synthesis of radiolabeled aromatic bisphosphonates and their potential application in bone metastasis pain palliation.
Biography
Biography: Marise Garcia Batlle
Abstract
Introduction: Bone metastases are the most frequent complication in the 80% of patients in advanced oncological stages. They are usually incurable, produce severe pain, decreasing the expectancy and quality of life of patients. Bisphosphonates are the main compounds employed for that purpose; nevertheless, their synthesis is relatively a complex process. The aim of the present work was to develop a simple synthesis method of aromatic bisphosphonates, potentially useful to alleviate metastatic bone pain, from their respective amino acids.
Materials and Methods: L-phenylalanine was used as starting material. The synthesis had three stages: 1) Protection of the amino group with a 1: 1 mixture of formic acid (98%) and acetic anhydride; 2) phosphonation of the protected phenylalanine with a mixture of H3PO3 and PCl5; 3) hydrolysis. The sodium salt of the 2-amino-3-phenyl-1-hydroxypropyl-1,1-bisphosphonic acid and the iodinated derivative thereof was obtained. The compounds obtained were characterized by infrared spectroscopy, 1H-NMR, 13C-NMR. The iodogen method was used for the labeling of the sodium salt obtained with 125I.
Results: The yield of the protection reaction of the amino group ranged between 75 and 80% and that of the phosphonation between 50 and 60%. All the compounds were obtained with a suitable purity evaluated by spectroscopic techniques.
Conclusions: A synthesis method was developed with novel modifications that allowed to obtain, both the sodium salt of the 2-amino-3-phenyl-1-hydroxypropyl-1,1-bisphosphonic acid, as well as the iodinated derivative thereof from the L -phenylalanine.