TECHNICAL ABSTRACTS 9:30 AM – 9:45 AM
“Design And Synthesis Of Novel Hemoglobin Crosslinks Based On Phosphonate Mimics On 2, 3‐Bisphosphoglycerate” Tigist W. Kassa, Jason S. Matthews, Faith A. Brown Department of Chemistry, Howard University, Washington, D.C. Abstract
Hemoglobin (Hb) being the natural oxygen carrier inside the red blood cell (RBC) has been the preferred choice for developing such substitute. However, there are two principal problems that must be overcome to utilize hemoglobin as a blood replacement. First, it suffers from short circulation times in the blood stream (1‐4hrs) due mainly to its breakdown from a large tetrameric protein, ʺ1ʺ2$1$2, into two smaller dimmer dimeric units, ʺ1$1 and ʺ2$2, resulting in its rapid renal elimination and afflicting considerably renal toxicity. Secondly, the increase in the oxygen affinity of hemoglobin because of the absence of 2,3‐bisphosphoglycerate limits the unloading of oxygen to the tissues. These drawbacks have been attributed to the loss of the natural allosteric effector of Hb, called 2,3 bisphosphoglycerate (BPG), upon isolation of pure stroma‐free Hb from RBC. We have designed compounds which mimic BPG outside RBC and can crosslink Hb tetramer in the $ cleft. ʺ,ʺ‐Difluoro substituted phosphonates are one class we intend to explore as 2, 3‐ bisphosphoglycerate analogues and have devised a synthetic scheme for. Squaric acid derivatives (squaramides) are a second class of phosphonate analogues that will be explored. These BPG analogues are expected to crosslink Hb dimmers at the positive amino acid sites where normally BPG stabilize the $ dimmers in RBC. 9:45 AM – 10:00 “Synthesis of Ether Derivatives of (S)‐Nicotine” AM Pauline W. Ondachi and Daniel L. Comins* Department of Chemistry, North Carolina State University, Dabney Hall, Campus Box 8204, Raleigh, NC Abstract Nicotine and its derivatives have in the recent past drawn a lot of interest due to their potential pharmacological role in the treatment of Central Nervous System (CNS) related diseases. One area of research the Comins group has been undertaking is development of novel methodologies for synthesis of enantiopure nicotine derivatives using commercially available (S)‐nicotine as a cheap starting material. A variety of acyclic and cyclic ether derivatives have been synthesized. Synthesis of C‐6 alkoxy derivatives was achieved through copper‐mediated reactions in two steps from (S)‐nicotine. Cyclic derivatives were 144