Structure Determination of a Chloroenyne from Laurencia majuscula Using Computational Methods and Total Synthesis

Despite numerous
advances in spectroscopic methods through the
latter part of the 20th century, the unequivocal structure determination
of natural products can remain challenging, and inevitably, incorrect
structures appear in the literature. Computational methods that allow
the accurate prediction of NMR chemical shifts have emerged as a powerful
addition to the toolbox of methods available for the structure determination
of small organic molecules. Herein, we report the structure determination
of a small, stereochemically rich natural product from Laurencia majuscula using the powerful combination
of computational methods and total synthesis, along with the structure
confirmation of notoryne, using the same approach. Additionally, we
synthesized three further diastereomers of the L. majuscula enyne and have demonstrated that computations are able to distinguish
each of the four synthetic diastereomers from the 32 possible diastereomers
of the natural product. Key to the success of this work is to analyze
the computational data to provide the greatest distinction between
each diastereomer, by identifying chemical shifts that are most sensitive
to changes in relative stereochemistry. The success of the computational
methods in the structure determination of stereochemically rich, flexible
organic molecules will allow all involved in structure determination
to use these methods with confidence.

尽管20世纪后期光谱学方法已取得诸多进展，但天然产物的明确结构鉴定仍颇具挑战，文献中也不可避免地出现过错误结构的报道。可精准预测核磁共振（NMR）化学位移的计算方法，已成为有机小分子结构鉴定工具库中极具价值的补充手段。本文报道了结合计算方法与全合成技术，对取自Laurencia majuscula的小型立体化学复杂型天然产物进行结构鉴定的研究，同时采用相同方法完成了notoryne的结构确证。此外，我们还合成了该L. majuscula来源烯炔类化合物的另外三种非对映异构体，并证实计算方法可从该天然产物的32种潜在非对映异构体中，精准区分出已合成的4种非对映异构体。本研究取得成功的关键在于：通过筛选对相对立体化学变化最为敏感的化学位移，分析计算数据以最大化不同非对映异构体之间的区分度。计算方法在立体化学复杂、具有柔性结构的有机分子结构鉴定中的成功应用，将使所有从事结构鉴定工作的研究人员能够放心地使用此类方法。