α-Glucosidase Inhibitory Activities and the Interaction Mechanism of Novel Spiro-Flavoalkaloids from YingDe Green Tea

Abstract

Flavoalkaloids are a unique class of compounds in tea, most of which have an N-ethyl-2-pyrrolidinone moiety substituted at the A ring of a catechin skeleton. 1-Ethyl-5-hydroxy-pyrrolidone, a decomposed product of theanine, was supposed to be the key intermediate to form tea flavoalkaloids. However, we have also detected another possible theanine intermediate, 1-ethyl-5oxopyrrolidine-2-carboxylic acid, and speculated if there are related conjugated catechins. Herein, four novel spiro-flavoalkaloids with a spiro-γ-lactone structural moiety were isolated from Yingde green tea (Camellia sinensis var. assamica) in our continuing exploration of new chemical constituents from tea. The structures of the new compounds, spiro-flavoalkaloids A-D (1−4), were further elucidated by extensive nuclear magnetic resonance (NMR) spectroscopy together with the calculated 13 C NMR, IR, UV−vis, highresolution mass, optical rotation, experimental, and calculated circular dichroism spectra. We also provided an alternative pathway to produce these novel spiro-flavoalkaloids. Additionally, their α-glucosidase inhibitory activities were determined with IC 50 values of 3.34 (1), 5.47 (2), 22.50 (3), and 15.38 (4) μM. Docking results revealed that compounds 1 and 2 mainly interacted with residues ASP-215, ARG-442, ASP-352, GLU-411, HIS-280, ARG-315, and ASN-415 of α-glucosidase through hydrogen bonds. The fluorescence intensity of α-glucosidase could be quenched by compounds 1 and 2 in a static style.

Two new catechins from Zijuan green tea enhance the fitness and lifespan of Caenorhabditis elegans via insulin-like signaling pathways

“…S23† and Table S8, ESI†) revealed the relative configuration of 1 to be Glc-4 S * with a high probability of approximately 100%. 44 Further, the ECD spectra of (2 R ,3 R ,Glc-1 S ,Glc-2 R ,Glc-3 S ,Glc-4 S ,Glc-5 R )- 1 and its enantiomer (2 R ,3 R ,Glc-1 S ,Glc-2 R ,Glc-3 S ,Glc-4 R ,Glc-5 R )- 1 were calculated at the LC-wPBE/6-311G(d,p) level with the Gaussian 09 software. 44 The experimental ECD spectrum of 1 fits well with the calculated spectrum of (2 R ,3 R ,Glc-1 S ,Glc-2 R ,Glc-3 S ,Glc-4 S ,Glc-5 R )- 1 (Fig.…”

“…44 Further, the ECD spectra of (2 R ,3 R ,Glc-1 S ,Glc-2 R ,Glc-3 S ,Glc-4 S ,Glc-5 R )- 1 and its enantiomer (2 R ,3 R ,Glc-1 S ,Glc-2 R ,Glc-3 S ,Glc-4 R ,Glc-5 R )- 1 were calculated at the LC-wPBE/6-311G(d,p) level with the Gaussian 09 software. 44 The experimental ECD spectrum of 1 fits well with the calculated spectrum of (2 R ,3 R ,Glc-1 S ,Glc-2 R ,Glc-3 S ,Glc-4 S ,Glc-5 R )- 1 (Fig. S24†), while being different from that of (2 S ,3 S ,Gal-1 R ,Gal-2 S ,Gal-3 R ,Gal-4 R ,Gal-5 S )- 1 .…”

“…S25† and Table S12, ESI†) revealed the relative configuration of 2 as 2 R *,3 R *,3′′′ S * with a high probability of 93.48%. 44 The ECD spectra of (2 R ,3 R ,3′′′ S )- 2 and its enantiomer were calculated at the LC-wPBE/6-311G(d,p) level with the Gaussian 09 software. 44 The experimental ECD spectrum of 2 fits well with the calculated spectrum of (2 R ,3 R ,3′′′ S )- 2 (Fig.…”

“…44 The ECD spectra of (2 R ,3 R ,3′′′ S )- 2 and its enantiomer were calculated at the LC-wPBE/6-311G(d,p) level with the Gaussian 09 software. 44 The experimental ECD spectrum of 2 fits well with the calculated spectrum of (2 R ,3 R ,3′′′ S )- 2 (Fig. 4), while being different from that of (2 S ,3 S ,3′′′ R )- 2 .…”

“…To determine the relative configurations of Glc-4 in 1, the 13 C NMR data of two potential isomers, (Glc-4S*)-1 and (Gal-4R*)-1, were calculated using the gauge-independent atomic orbital (GIAO) method at the mPW1PW91/6-311G (d,p) level with the Gaussian 09 software. 44 The results showed that (Glc-4S*)-1 had a better coefficient of determination (R 2 = 0.9747) of linear correlation between the experimental and calculated 13 C NMR data than (Gal-4R*)-1 (R 2 = 0.9730) (Fig. S23 †).…”