477565-90-5Relevant academic research and scientific papers
Concise Synthesis of Cinnamtannin A2 from Dimeric Epicatechin Electrophile and Nucleophile Prepared by Zn(OTf)2-Mediated Self-Condensation
Ichikawa, Mikihiro,Takanashi, Kohki,Suda, Manato,Hattori, Yasunao,Kawahara, Sei-Ichi,Fujii, Hiroshi,Makabe, Hidefumi
, p. 1525 - 1532 (2016)
The synthesis of cinnamtannin A2 from dimeric epicatechin nucleophile and electrophile was accomplished. Dimeric epicatechin nucleophile was prepared directly by reduction of the C-4′′ 1-ethoxy-?ethoxy group of the electrophile which was previously synthe
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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Page 8, (2008/06/13)
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.
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
Kozikowski, Alan P.,Tueckmantel, Werner,Boettcher, Gesine,Romanczyk Jr., Leo J.
, p. 1641 - 1658 (2007/10/03)
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.
