Chen Jianjun, Slominski Andrzej T, Miller Duane D, Li Wei
Department of Pharmaceutical Sciences; College of Pharmacy; University of Tennessee Health Science Center; Memphis, TN USA.
Department of Pathology and Laboratory Medicine and the Center for Cancer Research; University of Tennessee Health Science Center; Memphis, TN USA.
Dermatoendocrinol. 2013 Jan 1;5(1):142-9. doi: 10.4161/derm.24339.
Novel pregna-5, 7-dienes were synthesized and subjected to UVB irradiation to generate the corresponding pre-D intermediates, tachysterol and lumisterol analogs. The kinetics of the conversion from each of the pre-D intermediates to the corresponding novel D analogs was investigated by using real time 1H NMR measurements inside the NMR magnet. Both the length and composition of the side chains were found to affect the rate of the kinetic conversion from pre-D intermediates to the thermodynamically more stable D analogs. Compound 7cc which has both a long side chain and a tertiary alcohol moiety showed the highest conversion rate, while compound 4a-S which has a very short side chain without the tertiary alcohol had the lowest conversion rate among the 13 tested compounds. We also determined product distributions for these 5,7-dienes upon UVB irradiation followed by thermodynamic equilibration. No clear correlations between product distribution and side chain length or composition were identifiable under the current experimental conditions, suggesting there are other factors affecting the kinetics during the photochemical reactions for these 5,7-dienes. To the best of our knowledge, this is the first time the influences of side chain length and composition on the real time conversion kinetics from pre-D to D are studied. This study could serve as step-stones in future kinetic studies of novel biologically active 5,7-dienes and their corresponding D analogs under more physiologically relevant ex vivo or in vivo conditions, as well as providing important insights into optimizing yields of the desired active products during their organic syntheses.
合成了新型孕甾 -5,7 -二烯，并对其进行紫外线B照射以生成相应的前D中间体、速甾醇和光甾醇类似物。通过在核磁共振磁体内部使用实时¹H NMR测量，研究了从每种前D中间体转化为相应新型D类似物的动力学。发现侧链的长度和组成均会影响从前D中间体到热力学上更稳定的D类似物的动力学转化率。具有长侧链和叔醇部分的化合物7cc显示出最高的转化率，而具有非常短的侧链且没有叔醇的化合物4a - S在13种测试化合物中转化率最低。我们还确定了这些5,7 -二烯在紫外线B照射后进行热力学平衡时的产物分布。在当前实验条件下，未发现产物分布与侧链长度或组成之间存在明显的相关性，这表明在这些5,7 -二烯的光化学反应过程中存在其他影响动力学的因素。据我们所知，这是首次研究侧链长度和组成对从前D到D的实时转化动力学的影响。这项研究可以作为未来在更生理相关的离体或体内条件下对新型生物活性5,7 -二烯及其相应D类似物进行动力学研究的垫脚石，同时也为在其有机合成过程中优化所需活性产物的产率提供重要见解。
