**The Advanced Floating Chirality Distance Geometry Approach—How Anisotropic NMR Parameters Can Support the Determination of the Relative Configuration of Natural Products**

### **Matthias Köck 1,\*, Michael Reggelin 2 and Stefan Immel 2,\***


Received: 4 May 2020; Accepted: 18 June 2020; Published: 24 June 2020

**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.

**Keywords:** chirality; configurational analysis; distance geometry; NMR spectroscopy; NOE data; residual dipolar couplings
