Computer assisted structure elucidation of natural products using two-dimensional NMR spectroscopy†

Abstract

The ideal of computer assisted structure elucidation (CASE) is to generate, exhaustively and without redundancy, all possible structures that are consistent with a particular set of spectroscopic data. The aim is to achieve this goal with the minimum amount of human intervention. In natural product drug discovery the major bottleneck has always been structure elucidation, and it is with this in mind that the development of CASE began. Great advances have been made in this field in the past few years and programs that achieve most of these goals are currently available. The scope of this review is primarily to discuss the role of 2D NMR spectroscopy in CASE. Since this is a review for natural product chemists, the focus will be mainly on the use of these programs in solving complex natural product structures. The intended purpose of this review is not to be fully comprehensive, but rather to highlight different approaches to CASE and significant recent developments. It is also not the intention of the author to focus on the mathematical aspects of CASE, but instead to explain the concepts used in basic terms. The first part of the review highlights alternative approaches which either do not make use of 2D NMR data, or make use of them in a limited way. This is followed by the methods a natural product chemist may apply to elucidate the structure of a complex natural product. The next part of this review is structured in the same way that a CASE program fits together, and begins with a general description of the system, followed by details of the component parts. 2 Alternative approaches