The DP5 probability, quantification and visualisation of structural uncertainty in single molecules

Abstract

Whenever a new molecule is made, a chemist will justify the proposed structure by analysing the NMR spectra. The widely-used DP4 algorithm will choose the best match from a series...

Reassignment of Improbable Natural Products Identified through Chemical Principle Screening

“…[20] Furthermore, it is assumed that a correct structure is present, but can fail when SE predicts all incorrect structures in the top ranked list. DP5, [66] is a significant advance on DP4 as it relaxes the requirement that a set of potential candidate structures MUST have a correct structure among that set. That is, DP5 could indicate a candidate is the wrong structure with 100 % certainty regardless of whether there is a correct structure in the candidate set (i. e., the correct structure may arise with less than 100 % certainty).…”

Lycojapomines A–E: Lycopodium Alkaloids with Anti-Renal Fibrosis Potential from Lycopodium japonicum

“…In addition, DP5 has been shown to have a high performance in distinguishing diastereomers similar to that of DP4, although DP5 typically assigns similar probabilities to all of the diastereomers. 8 Both 2 and 7-epi-2 were subjected to DP5 considering the novel structure of this compound and, at this stage, no direct experimental evidence to rule out the latter. As a result, probabilities of 56.5% (2) and 72.7% (7-epi-2) were assigned (Figure 4).…”

“…To gain greater confidence in these structural assignments, and because our crystallization attempts failed, we applied DP5 probability analysis. 8 This newly developed computational method, unlike the currently widely used DP4 or DP4+, 9,10 can be used to calculate normalized stand-alone probabilities of one or multiple candidate structures being correct given 13 C NMR data and does not have to assume any of the structural proposals are correct. In addition, DP5 has been shown to have a high performance in distinguishing diastereomers similar to that of DP4, although DP5 typically assigns similar probabilities to all of the diastereomers.…”

“…This result could be interpreted as a confirmation of the planar structure; otherwise, the values would be much lower and typically close to zero. 8 However, the fact that DP5 indicated much greater confidence in 7-epi-2 and the probability value assigned (72.7%) was very close to maximum (73%) did confuse us a bit. When the NMR solvent was changed from methanol-d 4 to chloroform-d, H-7 turned to be a non-overlapping signal, which allowed for the confirmation of an NOE correlation of H-7/H-9 (Figure 3).…”

“…This newly developed computational method, unlike the currently widely used DP4 or DP4+, , can be used to calculate normalized stand-alone probabilities of one or multiple candidate structures being correct given 13 C NMR data and does not have to assume any of the structural proposals are correct. In addition, DP5 has been shown to have a high performance in distinguishing diastereomers similar to that of DP4, although DP5 typically assigns similar probabilities to all of the diastereomers . Both 2 and 7- epi - 2 were subjected to DP5 considering the novel structure of this compound and, at this stage, no direct experimental evidence to rule out the latter.…”