The use of indirectly bonded 13C-1H (INCH) shift correlation spectra for ab initio structure elucidation of natural products and other complex organic compounds; A personal and historical perspective

Abstract

This article reviews the use of long-range shift correlation spectra for structure elucidation of natural products and other complex organic compounds from the early 1980's to the present. Much of it is written from the personal viewpoint of someone who has been involved in this area of research since its earliest days. The first section covers the early use of long-range correlation spectra in the 1980's. The second section covers the development of specialized pulse sequences for this type of acquisition. It begins with three ¹³C-detected sequences, followed by heteronuclear multiple bond correlation (HMBC) and some modified versions of HMBC and, finally, longer range correlation sequences based on the heteronuclear single quantum multiple bond correlation sequence. The third section covers various sequences designed to distinguish between 2-bond and longer range ¹³C-¹H correlations. Unfortunately, none of these can make this distinction for non-protonated carbons. Only the 1,1-ADEQUATE sequence can make this distinction but its very low sensitivity limits its usefulness. The next section focuses on ways of avoiding getting incorrect structures of organic compounds, an ongoing problem in natural product research. The last section includes likely short-term developments and possible long-term developments in NMR methodology that would be beneficial for small molecule structure elucidation.