ACD/Structure Elucidator Featured Solution

In 2003, Philip Williams and co-workers¹ isolated a new cytotoxic peptide, Tasiamide B, from the marine cyanobacterium Symploca sp, which contained the unusual amino acid-derived residue 4-amino-3-hydroxy-5-phenylpentanoic acid (AHPPA). The structure of the peptide was determined through a combination of 2D NMR experiments and HPLC analysis of degradation products. The initial experimental data was then submitted to the Structure Elucidator Challenge to determine if the software could propose the same structure.

• The molecular formula of Tasiamide B was determined to be C₅₀H₇₄N₈O₁₂
• The following data were acquired:
  • 2D ¹H-¹H COSY (33 correlations), ¹H-¹³C HMBC (59 correlations)

The Molecular Connectivity Diagram produced by Structure Elucidator

• Initially, after 15 hours Structure Elucidator was unable to produce a structure consistent with the experimental data, which included 9 carbon atoms with sp² hybridization according to the authors’ findings.
• Since the ¹³C NMR showed only 46 signals instead of 50, it was deduced that molecule contained fragments exhibiting local symmetry. The authors deduced the presence of two monosubstituted phenyl rings.
• Two 1-AR (aromatic) fragments were introduced as User Fragments (UF) in the software, which promptly solved the structure in Fragment Mode in 23 seconds.
• Structure 1 ranked in the first position based on the lower dA value; the average deviation (dA) is a comparison between the experimental and predicted ¹³C chemical shifts.

Structure #1	Structure #2	Structure #3
dA = 1.227	dA = 1.781	dA = 1.843
dF = 2.113	dF = 2.253	dF = 2.573
dH = 0.188	dH = 0.206	dH = 0.242
dΣ = 3.122	dΣ = 3.841	dΣ = 4.261



Structure 1
• Structure 1 matches the structure published by the original authors who solved it by traditional means.

The addition of two 1-AR fragments helped to reduce the number of ambiguous connectivities and ultimately reduce the structures generation time. The ambiguity arises from the coincidental chemical shifts of hydrogen atoms in the aromatic region.

The problem demonstrates the benefits of introducing User Fragments which are easily revealed in the experimental data during the preliminary evaluation.

ACD/Structure Elucidator is a complete elucidation package offering tools to speed up the elucidation process and ensure that no candidate is overlooked. Learn more

d_F—the average deviation between the experimentally observed carbon chemical shifts and the carbon chemical shifts predicted using fast (increment based) prediction methods
d_H—the average deviation between the experimentally observed proton chemical shifts and the predicted proton chemical shifts using accurate (HOSE code based) prediction methods
d_Σ = d_A + 20-d_H—generalized match factor that takes into account deviations calculated by the accurate prediction methods both for ¹³C and ¹H NMR spectra