Abstract
The configurational analysis of complex natural products by NMR spectroscopy is still a challenging task. The assignment of the relative configuration is usually carried out by analysis of interproton distances from NOESY or ROESY spectra (qualitative or quantitative) and scalar (J) couplings. About 15 years ago, residual dipolar couplings (RDCs) were introduced as a tool for the configurational determination of small organic molecules. In contrast to NOEs/ROEs which are local parameters (distances up to 400 pm can be detected for small organic molecules), RDCs are global parameters which allow to obtain structural information also from long-range relationships. RDCs have the disadvantage that the sample needs a setup in an alignment medium in order to obtain the required anisotropic environment. Here, we will discuss the configurational analysis of five complex natural products: axinellamine A (1), tetrabromostyloguanidine (2), 3,7-epi-massadine chloride (3), tubocurarine (4), and vincristine (5). Compounds 1–3 are marine natural products whereas 4 and 5 are from terrestrial sources. The chosen examples will carefully work out the limitations of NOEs/ROEs in the configurational analysis of natural products and will also provide an outlook on the information obtained from RDCs.
Highlights
The determination of the relative and absolute configuration of natural products is essential to understand their interactions in the biological field and to allow their procurement through total synthesis
The residual dipolar couplings (RDCs) data for 5 were taken from Ref. [22] for three stereogenic centers, six of which are arranged consecutively in a six-membered ring and three are independent alignment scenarios, respectively. It located in a remote ring fragment connected to the former segment by a single rotatable bond only, must be noted that due to the absence of NOE and RDC associated with the substituents of C-42
Using NOE data only, the carrying a hydroxyl group and a COOMe ester moiety), the configuration of this stereogenic center is first wrong structure is already the structure No #1 ranked best, not assignable based on the data used here, and C-42 was excluded from any further analysis
Summary
The determination of the relative and absolute configuration of natural products is essential to understand their interactions in the biological field and to allow their procurement through total synthesis. The structure determination of natural products by NMR spectroscopy [1,2,3] is usually divided into two more or less “independent” approaches: (a) constitutional assignment and (b) configurational and conformational assignment (see Figure 1). The constitutional assignment will not be covered in the present manuscript. We will focus on the discussion of the assignment of the relative configuration and conformation only. Mar. Drugs 2020, 18, 330; doi:10.3390/md18060330 www.mdpi.com/journal/marinedrugs
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