Solution Conformation of Flexible Organic Molecules

本计画的目的是发展新的演算法，以应用于构象分析中多重最小值问题的计算研究，并进行编码，以及将程式应用于实际问题。在计画期末，所有这些目的都已达成。一个全新的演算法，称为Corner Flapping，可以系统地产生所有可能的环构象。这种算法很可能是所有现有方法中最快的。用于执行Corner Flapping的程序CONFLEX 2的第二个版本已存放在公共领域（QCPE #592、JCPE #21）。在撰写本报告时，该算法的扩展修改CONFLEX3几乎已经准备就绪。此外，对Karplus方程进行了广泛的修改，并且用于执行多参数方程的程序3JHHM已经被存放在公共领域（QCPE #591，JCPE #12）。 关于我们 有机化学实验中遇到的问题。令人惊讶的是，已经发现了大量的新构象与三环[9.3.1.0 ^<3.8>]十五烷的CONFLEX 2，著名的天然产物紫杉醇的母体骨架。利用CONFLEX 2方法获得的大量最小能量构象，对烟草叶虫性信息素丝角宁的活性构象进行了估算。对Leuconglutamine A合成中的一个重要的16元环中间体进行CONFLEX 2，以获得化学上显著的构象。这一大规模计算的成功完成，从而打开了大门，攻击类似的问题，如分析伍德沃德的内酯封闭反应在红霉素的全合成。最后，我们感兴趣的是确定天然产物的三维结构的组合，修改后的Karplus方程，3JHHM和MM。该方法是使用过乙酸酯的小aiditols作为模型。到目前为止，成功率达到92%。少

The purposes of this project is to develop new algorithms useful for the computational investigation of the multi-minimum problem in conformational analysis, to perform coding, and to apply the programs to the practical problems.By the end of the proposed term of project, all these purposes have been achieved.An entirely new algorithm, called Corner Flapping, for systematically generating all possible ring conformations was developed. It is likely that this algorithm will be the fastest of all the existing methods. The second version of the program CONFLEX2 for the execution of Corner Flapping has been deposited in public domain (QCPE #592, JCPE #21). An expanded modification of this algorithm, CONFLEX3, is almost ready at the time of writing this report. In addition, Karplus equation was extensively modified and a program for executing the multiparametric equation, 3JHHM, has been deposited in public domain (QCPE #591, JCPE #12).These computational tools have been applied to a number … More of problems encountered in experimental organic chemistry. Surprisingly large number of new conformers have been found with CONFLEX2 for tricyclo[9.3.1.0^<3.8>]pentadecane, parent skeleton of the noted natural product taxin. Active conformations of sericornine, a sex pheromone for tobacco leaf bugs, have been estimated based on a large number of energy-minimum conformers obtained by CONFLEX2. An important 16-membered ring intermediate in the synthesis of Leuconolide A was subjected to CONFLEX2 in order to obtain thermodynamically significant conformations. This large scale calculation was successfully completed, and thus opened a door to attacking similar problems, such as the analysis of Woodward's lactone closure reaction in the total synthesis of erythromycin. Finally, we are interested in determining three-dimensional structure of natural products by the combination of modified Karplus equation, 3JHHM and MM. The methodology was developed using peracetates of small aiditols as models. A success rate of 92% has so far been achieved. Less