TY - JOUR
T1 - Total syntheses of schizandriside, saracoside and (±)-isolariciresinol with antioxidant activities
AU - Sampei, Mana
AU - Arai, Midori A.
AU - Ishibashi, Masami
N1 - Funding Information:
Acknowledgements This study was supported by KAKENHI Grant numbers 17H03992 and 15H04650, Suzuken Memorial Foundation, Takeda Science Foundation, Astellas Foundation for Research on Metabolic Disorders, the Naito Foundation, Strategic Priority Research Promotion Program, Chiba University, ‘Phytochemical Plant Molecular Sciences’, JSPS A3 Foresight Program, and a Workshop on Chirality at Chiba University (WCCU). This work was inspired by the international and interdisciplinary environment of the JSPS Core-to-Core Program ‘Asian Chemical Biology Initiative’.
Publisher Copyright:
© 2018, The Japanese Society of Pharmacognosy and Springer Japan KK, part of Springer Nature.
PY - 2018/6/1
Y1 - 2018/6/1
N2 - Lignans are widely distributed in plants and exhibit significant pharmacological effects, including anti-tumor and antioxidative activities. Here, we describe the total synthesis of schizandriside (1), a compound we previously isolated from Saraca asoca by monitoring antioxidative activity using the 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay. Starting from a tandem Michael-aldol reaction, the lignan skeleton was synthesized in 6 steps, including a cyclization step. To determine the stereochemistry of 1, we synthesized the natural product (±)-isolariciresinol (18) from alcohol 17. Comparison of the spectral data showed good agreement. Glycosylation was investigated using four different glycosyl donors. Only the Koenigs–Knorr condition using silver trifluoromethanesulfonate with 1,1,3,3-tetramethylurea provided the glycosylated product. Deprotection and purification using reverse-phase high-performance liquid chromatography gave schizandriside (1) and its diastereomer saracoside (2). Synthesized 1, 2 and 18 showed antioxidant activity with IC50 = 34.4, 28.8, 53.0 μM, respectively.
AB - Lignans are widely distributed in plants and exhibit significant pharmacological effects, including anti-tumor and antioxidative activities. Here, we describe the total synthesis of schizandriside (1), a compound we previously isolated from Saraca asoca by monitoring antioxidative activity using the 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay. Starting from a tandem Michael-aldol reaction, the lignan skeleton was synthesized in 6 steps, including a cyclization step. To determine the stereochemistry of 1, we synthesized the natural product (±)-isolariciresinol (18) from alcohol 17. Comparison of the spectral data showed good agreement. Glycosylation was investigated using four different glycosyl donors. Only the Koenigs–Knorr condition using silver trifluoromethanesulfonate with 1,1,3,3-tetramethylurea provided the glycosylated product. Deprotection and purification using reverse-phase high-performance liquid chromatography gave schizandriside (1) and its diastereomer saracoside (2). Synthesized 1, 2 and 18 showed antioxidant activity with IC50 = 34.4, 28.8, 53.0 μM, respectively.
KW - Antioxidant activity
KW - Lignan glycoside
KW - Natural product
KW - Total synthesis
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U2 - 10.1007/s11418-018-1198-6
DO - 10.1007/s11418-018-1198-6
M3 - Article
C2 - 29508253
AN - SCOPUS:85045145754
SN - 1340-3443
VL - 72
SP - 651
EP - 654
JO - Journal of Natural Medicines
JF - Journal of Natural Medicines
IS - 3
ER -