- Synthesis of procyanidins C2 and C1 using lewis acid mediated equimolar condensation
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Synthesis of procyanidins C2 and C1 was achieved via a stereoselective intermolecular condensation of equimolar amount of dimeric catechin or epicatechin nucleophile and monomeric catechin or epicatechin electrophile using Lewis acid. In the case of synthesis of procyanidin C2, AgBF4 and AgOTf afforded condensed product in excellent yield. As to the synthesis of procyanidin C1, Yb(OTf)3 was effective for equimolar condensation.
- Oizumi, Yukiko,Katoh, Miyuki,Makabe, Hidefumi,Hattori, Yasunao,Toda, Kazuya,Kawaguchi, Koichiro,Fujii, Hiroshi
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p. 2241 - 2250,10
(2020/08/31)
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- Synthesis of dimeric, trimeric, tetrameric pentameric, and higher oligomeric epicatechin-derived procyanidins having 4beta,8-interflavan linkages and their use to inhibit cancer cell growth through cell cycle arrest
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Various processes are disclosed for preparing protected epicatechin oligomers having (4β,8)-interflavan linkages. In one process, a tetra-O-protected epicatechin monomer or oligomer is coupled with a protected, C-4 activated epicatechin monomer in the presence of an acidic clay such as a mortmorillonite clay. In another process, a 5,7,3′,4′-benzyl protected or a 3-acetyl-, 5,7,3′,4′-benzyl protected epicatechin or catechin monomer or oligomer is reacted with 3-O-acetyl-4-[(2-benzothiazolyl)thio]-5,7,3′,4′-tetra-O-benzylepicatechin in the presence of silver tetrafluoroborate. In another process, two 5,7,3′,4′-benzyl protected epicatechin monomers activated with 2-(benzothiazolyl)thio groups at the C-4 positions are cross-coupled in the presence of silver tetrofluoroborate. A process is also disclosed for reacting an unprotected epicatechin or catechin monomer with 4-(benzylthio) epicatechin or catechin. The use of naturally-derived and synthetically-prepared procyanidin (4β,8)4-pentamers to treat cancer is also disclosed.
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- Efficient stereoselective synthesis of proanthocyanidin trimers with TMSOTf-catalyzed intermolecular condensation
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A stereoselective synthesis of seven benzylated proanthocyanidin trimers with TMSOTf-catalyzed condensation reaction is described. In particular, epicatechin-(4β-8)-epicatechin-(4β-8)-epicatechin trimer (procyanidin C1), catechin-(4α-8)-catechin-(4α-8)-catechin trimer (procyanidin C2), epicatechin-(4β-8)-epicatechin-(4?-8)-catechin trimer and epicatechin-(4?-8)-catechin-(4α-8)-epicatechin trimer derivatives were obtained in excellent yields. The structure of benzylated procyanidin C2 was confirmed by comparing the 1H NMR spectra of protected procyanidin C2 that was synthesized by two different condensation approaches. Finally, deprotection of (+)-catechin and (-)-epicatechin trimers derivatives gave four natural procyanidin trimers in good yields.
- Saito, Akiko,Tanaka, Akira,Ubukata, Makoto,Nakajima, Noriyuki
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p. 1069 - 1073
(2007/10/03)
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- Systematic synthesis of four epicatechin series procyanidin trimers and their inhibitory activity on the Maillard reaction and antioxidant activity
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A systematic synthesis of four natural epicatechin series procyanidin trimers {[4,8:4″,8″]-2,3-cis-3,4-trans: 2″,3″-cis- 3″,4″-trans: 2′?,3′?-trans-(-)-epi- catechin-(-)-epicatechin-(+)-catechin, [4,8:4″,8″]-2,3-cis-3,4- trans: 2″,3″-cis-3″,4″-trans: 2′?, 3′?-cis-tri-(-)-epicatechin: procyanidin C1, [4,8:4″, 8″]-2,3-cis-3,4-trans: 2″,3″-trans-3″,4″-trans: 2′?,3′?-trans-(-)-epicatechin-(+)-catechin-(+) -catechin: procyanidin C4, and [4,8:4″,8″]-2,3-cis-3,4-trans: 2″,3″-trans-3″,4″-trans: 2′?, 3′?-cis-(-)-epicatechin-(+)-catechin-(-)-epicatechin} is described. Condensation of (2R,3R,4S)-5,7,3′4′-tetra-O-benzyl-4-(2″- ethoxyethyloxy)flavan derived from (-)-epicatechin as an electrophile with the dimeric nucleophiles in the presence of TMSOTf followed by deprotection yielded trimers. Inhibitory activities on the Maillard reaction and antioxidant activity on lipid peroxide of the synthesized oligomers were also investigated.
- Saito, Akiko,Doi, Yuki,Tanaka, Akira,Matsuura, Nobuyasu,Ubukata, Makoto,Nakajima, Noriyuki
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p. 4783 - 4790
(2007/10/03)
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- Studies in polyphenol chemistry and bioactivity. 4. Synthesis of trimeric, tetrameric, pentameric, and higher oligomeric epicatechin-derived procyanidins having all-4β,8-interflavan connectivity and their inhibition of cancer cell growth through cell cycle arrest
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We report an improved synthesis of bis(5,7,3′,4′-tetra-O-benzyl)epicatechin 4β,8-dimer (3) from 5,7,3′,4′-tetra-O-benzylepicatechin (1) and 5,7,3′,4′-tetra-O-benzyl-4-(2-hydroxyethoxy)epicatechin (2) by replacing the previously employed Lewis acid, titanium tetrachloride, with the clay mineral Bentonite K-10. Under the same conditions, the benzyl-protected all-4β,8-trimer, -tetramer, and -pentamer were obtained regioselectively from their lower homologues, albeit in rapidly decreasing yields. Reaction of 2 with an organoaluminum thiolate generated from 2-mercaptobenzothiazole and trimethylaluminum followed by acetylation produced 3-O-acetyl -4-[(2-benzothiazolyl)thio]5,7,3′,4′-tetra-O-benzylepicatechin (12). Medium-sized protected oligomers with 4β,8-interflavan linkages are obtained in improved yields by using this compound as the electrophile and silver tetrafluoroborate as activator and are isolated by reversed-phase HPLC. Their deprotection by ester saponification followed by hydrogenolysis yielded the free procyanidins, which were characterized as their peracetates. The synthetic procyanidins are identical by normal-phase HPLC with fractions isolated from cocoa. The principle of chain extension by two members was demonstrated using a dimeric electrophile obtained by self-condensation of compound 12. Both the synthetic and natural pentamer 32 inhibit the growth of several breast cancer cell lines. Using the MDA MB 231 line, it was established that this outcome is based on the induction of cell cycle arrest in the G0/G1 phase. Subsequent cell death is more likely necrotic rather than apoptotic. Control experiments demonstrate that the polyphenol itself, rather than hydrogen peroxide potentially formed by its autoxidation, is the causative agent.
- Kozikowski, Alan P.,Tueckmantel, Werner,Boettcher, Gesine,Romanczyk Jr., Leo J.
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p. 1641 - 1658
(2007/10/03)
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