256236-25-6Relevant articles and documents
Scale-Up Syntheses of Two Naturally Occurring Procyanidins: (-)-Epicatechin-(4β,8)-(+)-catechin and (-)-Epicatechin-3-0-galloyl- (4β, 8)-(-)-epicatechin-3-0-gallate
Sharma, Pradeep K.,Kolchinski, Alexander,Shea, Helene A.,Nair, Jayesh J.,Gou, Yanni,Romanczyk Jr., Leo J.,Schmitz, Harold H.
, p. 422 - 430 (2012/12/31)
A scaleable process for the synthesis of two naturally occurring procyanidins, namely (-)-epicatechin-(4β,8)-(+)-catechin (1) and(-)-epiratechin-3-O-galloyl-(4β,8)-(-)-epicatechin-3-O-gallate (2), is described. The key steps were highlighted by improvements for the benzylation of (+)-catechin (3), stereo-selective reduction of the C-3 keto group of (2A)-5,7,3′,4′-tetrakis(benzyloxy)flavan-3-one (10), and coupling between 4-hydroxyethoxy-5,7,3′,4′-tetra-O-benzyl-(-)-epicatechin (11) and 5,7,3′,4′-tetra-O-benzyl-(+)-catechin (4) or 5,7,3′,4′-tetra-O-benzyl-(-)-epicatechin (6), respectively. The debenzylation performed in a biphasic system resulted in an improved yield and purity of the target compounds. The chemistry was scaled-up to produce multigram quantities of the title compounds (1 and 2) for various in vitro, ex vivo, and in vivo studies. Moreover, the scale-up process provided a detailed description for the preparation of multihundred to kilogram scale quantities of intermediates used in the synthesis of these two titled procyanidins.
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 6, (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. 1. Preparation of building blocks from (+)-catechin. Procyanidin formation. Synthesis of the cancer cell growth inhibitor, 3-O-galloyl-(2R,3R)-epicatechin-4β,8-[3-O-galloyl-(2R,3R)-epicatechin]
Tueckmantel, Werner,Kozikowski, Alan P.,Romanczyk Jr., Leo J.
, p. 12073 - 12081 (2007/10/03)
A project has been initiated to synthesize proanthocyanidin oligomers found in cocoa. Natural, readily available (+)-catechin was transformed into 5,7,3′,4′-tetra-O-benzyl-(-)-epicatechin (14) by (a) benzylation of the phenolic oxygens; (b) oxidation of the 3-alcohol to ketone by the Dess-Martin periodinane; and (c) reduction with lithium tri-sec-butylborohydride (L-Selectride) in the presence of LiBr. The additive diminishes the extent of ketone enolization while maintaining a stereoselectivity of ≥ 200:1. Oxidation of 14 with DDQ was performed best from the standpoint of product purification if ethylene glycol was used as the nucleophilic trapping agent. The resulting ether 19 was condensed with 14 using TiCl4 to give a good yield of benzyl-protected epicatechin-4β,8-epicatechin (octa-O-benzylprocyanidin B2, 20) as the sole dimeric product. Hydrogenolysis of 20 yielded procyanidin B2 in the first enantiospecific synthesis of this natural product which employs protected intermediates and thereby allows the necessary product separation after the condensation step to be performed on nonpolar, nonsensitive intermediates. Acylation of 20 with tri-O-benzylgalloyl chloride followed by hydrogenolysis gave access to the title bis-gallate (24). This constitutes the first synthesis of this natural product, a compound notable for its PKC-inhibitory and anticancer activity.
