Synthetic Studies toward 5,6,7,3′,4′-Monomethoxytetrahydroxyflavones: Synthesis of Pedalitin
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Published:2024-01-19
Issue:2
Volume:29
Page:513
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ISSN:1420-3049
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Container-title:Molecules
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language:en
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Short-container-title:Molecules
Author:
Kamma Koteswara Rao1, Cho Joungmo2ORCID, Won Hyo Jun3, Nam So-Yeon1, Le Ngan Hong2, Jung Je Hyeong3ORCID, Lee Kee-In12ORCID
Affiliation:
1. Research and Development Center, Molecules & Materials Co., Ltd., Daejeon 34013, Republic of Korea 2. Green Chemistry Division, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea 3. Smart Farm Research Center, Korea Institute of Science and Technology, Gangneung 25451, Republic of Korea
Abstract
During the synthetic studies toward 5,6,7,3′,4′-monomethoxytetrahydroxyflavones, a concise pedalitin synthesis procedure was achieved. As previously reported, 6-hydroxy-2,3,4-trimethoxyacetophenone was prepared by Friedel–Crafts acylation of 1,4-dihydroxy-2,6-dimethoxybenzene with boron trifluoride diethyl etherate in acetic acid. When aldol condensation of 6-hydroxy-2,3,4-trimethoxyacetophenone 2b with vanillin was performed in basic conditions, it produced 2′-hydroxychalcone 3b, and, surprisingly, along with 3-hydroxyflavone 4 in a considerable amount. We propose that this oxidative cyclization is presumably due to the contribution of a quinone methide, likely to be subjected to aerobic oxidation. The chalcone was then subjected to oxidative cyclization with iodine in dimethyl sulfoxide to afford flavone 5 in good yield. To our delight, serial demethylation of the three methoxy groups at the 5-, 6-, and 3′-positions of 5 proceeded smoothly to produce pedalitin 1, under hydrogen bromide solution (30% in acetic acid). The crystal structures of 3-hydroxyflavone 4 and pedalitin tetraacetate 6 were unambiguously determined by X-ray crystallography.
Funder
Korea Institute of Science and Technology Materials/Parts Technology Development Program Ministry of Trade, Industry & Energy, Republic of Korea
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
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