Surface Modified Zirconia as Chiral Stationary Phases

描述（由申请人提供）：我们的第一阶段工作解决了HPLC当前的主要趋势之一-开发用于改进手性色谱的材料。为此，我们制备了两类新的手性固定相（csp）。我们制备了10个不同类型的例子，其中手性选择器与碳包覆氧化锆表面共价键合。此外，我们制备了26种不同的第二类CSP变体，其中手性选择器通过刘易斯酸/碱配位共价锚基团连接到氧化锆表面。我们发现第二类相通常比第一类相具有更好的手性选择性，并且基于相关的手性选择器与商业相非常相似。鉴于氧化锆的表面化学性质非常不同，我们认为氧化锆基相与胺化药物的Bronsted表面酸碱反应将比硅基相严重得多。由于这些原因，第二阶段的工作将集中在开发新开发的Lewis酸碱锚定csp上。我们在第二阶段的四个主要目标是：将第一阶段的3微米分析HPLC颗粒扩展到5、7、10和25微米颗粒，用于半制备和预制备规模的LC，扩大生产规模，以更大的批量生产，表征这些更大的颗粒的关键色谱特性(手性选择性，负载能力，最后合成了一系列的Whelk O - 1样和α - burke 2仿真相，可用于新HPLC方法开发中的手性选择器快速筛选，以快速确定最合适的手性选择器类型。为了实现这些目标，我们将把合成工作分包给明尼苏达大学的Tom Hoye教授，他是天然产物合成化学领域的国际专家。

DESCRIPTION (provided by applicant): Our phase I work addressed one of the major current trends in HPLC - the development of materials for improved chiral chromatography. In response, we prepared two new classes of chiral stationary phases (CSPs). We prepared 10 different examples of the class wherein the chiral selector is covalently bonded to the surface of carbon-clad zirconia. Additionally, we prepared 26 different variants of the second class of CSP wherein the chiral selectors is bonded to the surface of zirconia through a Lewis acid/base coordinate covalent anchor group. We found that the second class of phase generally has much better chiral selectivity than the first and was very comparable to commercial phases based on related chiral selectors. Given the very different surface chemistry of zirconia we believe that Bronsted surface acid-base reactions with aminated drugs will be much less serious issues with zirconia based phases compared to silica-based phases. For these reasons phase II work will center on exploiting the newly developed Lewis acid-base anchored CSPs. Our four principal aims in phase II are: to extend our phase I work on 3 micron analytical HPLC particles unto 5, 7,10 and 25-micron particles for semi-prep and prep-scale LC, to scale-up production to the larger batch sizes, to characterize these larger particles made in bigger batches for their critical chromatographic properties (chiral selectivity, loading capacity, efficiency) and last to synthesize a series of Whelk O 1-like and alpha-Burke 2 emulator phases that can be used for rapid chiral selector screening in new HPLC method development to quickly determine the most appropriate type of chiral selector. To accomplish these goals we will subcontract the synthetic efforts to Prof. Tom Hoye of the University of Minnesota an international expert in the area of natural products synthetic chemistry.