A grayanotox-9(11)-ene derivative from Rhododendron brachycarpum and its structural assignment via a protocol combining NMR and DP4 plus application.
A growing body of evidence points to the useful roles of computational approaches in the structural characterization of natural products. Rhododendron brachycarpum has been traditionally used for the control of diabetes, hepatitis, hypertension, and rheumatoid arthritis and classified as an endangered species in Korea. A grayanotox-9(11)-ene derivative along with five known diterpenoids, were isolated from the MeOH extract of R. brachycarpum. Extensive 1D and 2D NMR experiments were conducted to establish the 2D structure and relative configuration of the grayanotox-9(11)-ene derivative. Comparison of simulated and experimental ECD spectra resulted in an inconclusive outcome to assign its absolute configuration. Alternatively, gauge-including atomic orbitals (GIAO) NMR chemical shift calculations, with support by the advanced statistical method DP4 plus, and acid hydrolysis were employed to establish its absolute configuration. This work exemplifies how NMR analysis, combined with quantum mechanics calculations, is a viable approach to accomplish structural assignment of minor abundance molecules in lieu of X-ray crystallography or chiroptical approaches.
College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea; Phutho College of Pharmacy, Viettri City, Phutho Province, Viet Nam.
Nguyen Quoc
NQ
Tuan
Department of BioMolecular Sciences, Division of Pharmacognosy, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, MS 38677, United States; Department of Chemistry, Yale University, New Haven, CT 06520, United States; Chemical Biology Institute, Yale University, West Haven, CT 06516, United States.
Joonseok
J
Oh
Department of Chemistry, Yale University, New Haven, CT 06520, United States; Chemical Biology Institute, Yale University, West Haven, CT 06516, United States.
Hyun Bong
HB
Park
Department of BioMolecular Sciences, Division of Pharmacognosy, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, MS 38677, United States.
Daneel
D
Ferreira
Forensic Toxicology Division, National Forensic Service, Wonju 220-170, Republic of Korea.
Sanggil
S
Choe
Forensic Toxicology Division, National Forensic Service, Wonju 220-170, Republic of Korea.
Juseon
J
Lee
College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea. Electronic address: mkna@cnu.ac.kr.
MinKyun
M
Na
D001412:Bacillus subtilis / Q000187:drug effects; D018360:Crystallography, X-Ray; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification*; D004926:Escherichia coli / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010946:Plants, Medicinal / Q000737:chemistry*; D056910:Republic of Korea; D029793:Rhododendron / Q000737:chemistry*
D004224:Diterpenes
DP4 plus; Electronic circular dichroism; Endangered plant species; Gauge-including atomic orbitals NMR chemical shift calculations; Rhododendron brachycarpum; Stereochemical assignments