Isolation, absolute configuration determination and αlpha glucosidase inhibitory activity of labdane diterpenoids from Hedychium coronarium J. Koenig Rhizomes and LCMS profiling of Alpinia purpurata (Vieill.) K. Schum rhizomes / Maryam Kemi Gafar
The necessitation of stereochemical study of chiral drugs to ensure their safety before manufacturing have spurred the need to determine the absolute configuration (AC) of labdane diterpenoids isolated from rhizomes of Hedychium coronarium J. Koenig. Literature has revealed that NMR data alone ar...
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| Format: | Thesis |
| Language: | English |
| Published: |
2020
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| Online Access: | https://ir.uitm.edu.my/id/eprint/61105/1/61105.pdf |
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| Summary: | The necessitation of stereochemical study of chiral drugs to ensure their safety before
manufacturing have spurred the need to determine the absolute configuration (AC) of
labdane diterpenoids isolated from rhizomes of Hedychium coronarium J. Koenig.
Literature has revealed that NMR data alone are insufficient for stereochemical study
of these compounds. The employment of CD technique such as vibrational circular
dichroism (VCD) along with density functional theory (DFT) calculations has helped
to unequivocally assign AC of stereogenic centers of labdane diterpenoids from other
plants. Labdane diterpenoids are known to possess α-glucosidase inhibitory activity
but there is no report of this activity of the labdane diterpenoids isolated from the
rhizomes of the Hedychium coronarium. Alpinia purpurata (Vieill.) K. Schum
rhizomes have been reported to contained few labdane diterpenoids. However, no
report on LCMS profile of fractions from rhizomes of this plant with a view of
identifying more labdane diterpenoids. This study was aimed at the isolation,
purification and characterization of labdane diterpenoids from Hedychium coronarium
rhizomes through RHPLC method, NMR, FT-IR, OR and MS analyses, and the
determination of the distribution of labdane diterpenoids in Alpinia purpurata
rhizomes by qualitative LCMS profiling of its Hexane and DCM fractions.
Experimental and theoretical vibrational circular dichroism (VCD) analyses were
conducted on the isolated labdane diterpenoids. Conformational analysis was carried
out by MMFF94 as implemented in Spartan 14 software. The stable conformers of
less than 10 kcal and higher than 1.5% Boltzmann population were geometrical
optimized at DFT/B3LYP/6-31+G(d,p) level of theory as implemented in Gaussian
16. Two new C-15 diastereotopic labdane diterpenoids; Hα-15 (15R) and Hβ-15 (15S)
Coronarin D methyl ethers (Compound I and II) were successfully separated and their
absolute configurations were unequivocally established as (+)-(5S,9S,10S,15R) and (-
)-(5R,9R,10S,15S), respectively. The two compounds gave four theoretical stable
conformers each along with their relative energies and Boltzmann populations at
298K. Nine other known labdane diterpenoids; Compound III to X and XII were also
isolated and absolute configurations of four of them (Compound IV, V, VIII and XII)
were established as (+)-(5S,9S,10S)-labda-8(17),13(14)-diene-16,15-olide, (+)-
(5S,9S,10S)-labda-8(17),12-diene-15(16)-olide, (-)-(5R,9S,10S,11S,15S)-15-hydroxy-
16-formy-labda-8(17),12-dien-11,15-peroxide and (+)-(5S,9S,10S)-15,16-bisnorlabda-
8(17),11-diene-13-one, respectively. Compound III and IX; Coronarin D C-15
epimers and 15-hydroxy-labda-8(17),13(14)-diene-16,15-olide or Coronarin C
epimers were established by VCD as C-15 epimeric mixtures. The two new labdane
diterpenoids along with seven others from Hedychium coronarium rhizomes were
subjected to α-glucosidase inhibitory assay. Six compounds; I, II, IV, VIII, IX and X
showed the most significant α-glucosidase inhibitory activity with compound II being
the most active with IC50 of 22 μM; twice as effective as than acarbose with IC50 of 46
μM. All the compounds (I, II, IV, VIII, IX and X) are hits for α-glucosidase inhibitors
for management of diabetes mellitus. The qualitative LCMS profiling of the Alpinia
purpurata rhizomes fractions revealed ten and eleven possible labdane diterpenoids
from hexane and DCM fractions, respectively. |
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