137550-06-2

Upstream product

• 20728-73-8 5,7,3',4'-tetra-O-benzyl-(+)-catechin 
• 294203-72-8 (2R,3S,4S)-5,7,3',4'-tetrabenzyloxy-4-methoxyflavan-3-ol 
• 664351-41-1 (2R,3S,4S)-3-acetoxy-5,7,3',4'-tetrabenzyloxy-4-(2-ethoxyethoxy)flavan 
• 1217257-69-6 3’,4’,5,7-tetra-O-benzyl-4β-O-propargylcatechin 
• 476312-06-8 [4,8']-2,3-trans-3,4-trans:2',3'-trans-octa-O-benzyl-3-O-acetyl-bi-(+)-catechin 
• 137624-11-4 (2R,3S,4S)-5,7-Bis-benzyloxy-2-(3,4-bis-benzyloxy-phenyl)-chroman-3,4-diol 

Downstream Products

• 23567-23-9 procyanidin B₃ 
• 828249-33-8 [4,8’]-2,3-trans-3.4-trans:2’,3’-trans-octabenzyloxy-(+)-catechin-3-(tribenzyloxy)gall 
• 223387-33-5 [4,8’]-2,3-trans-3.4-trans:2’,3’-trans-Octabenzyloxy-bi-(+)-catechin-3,3”-di-(tribenzyloxy)gallate 

Relevant academic research and scientific papers

Synthesis of procyanidin B3 and its anti-inflammatory activity. the effect of 4-alkoxy group of catechin electrophile in the Yb(OTf)3-catalyzed condensation with catechin nucleophile

(Figure Presented) Yb(OTf)3-catalyzed equimolar condensation of the benzylated catechin with various 4-alkoxy catechin derivatives was studied. In particular, the reaction using 4-(2′′-ethoxyethoxy)flavan derivative gave good yield with excellent stereoselectivity. The condensed product was successfully converted to procyanidin B3 (1). The anti-inflammatory effect of procyanidin B3 (1) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation of mouse ears was examined. The anti-inflammatory activity of 1 was stronger than that of indomethacin and glycyrrhetinic acid, the normally used anti-inflammatory agents.

Enhanced radical scavenging activity of a procyanidin B3 analogue comprised of a dimer of planar catechin

Proanthocyanidins are oligomers of catechins that exhibit potent antioxidative activity and inhibit binding of oxidized low-density lipoprotein (OxLDL) to the lectin-like oxidized LDL receptor (LOX-1), which is involved in the onset and development of arteriosclerosis. Previous attempts aimed at developing proanthocyanidin derivatives with more potent antioxidative activity and stronger inhibition for LOX-1 demonstrated the synthesis of a novel proanthocyanidin derivative (1), in which the geometry of one catechin molecule in procyanidin B3 was constrained to a planar orientation. The radical scavenging activity of 1 was 1.9-fold higher than that of procyanidin B3. Herein, we synthesized another procyanidin B3 analogue (2), in which the geometries of both catechin molecules in the dimer were constrained to planar orientations. The radical scavenging activity of 2 was 1.5-fold higher than that of 1, suggesting that 2 may be a more effective candidate than 1 as a therapeutic agent to reduce oxidative stress induced in arteriosclerosis or related cerebrovascular disease.

Synthetic studies of proanthocyanidins. Part 5.1 Highly stereoselective synthesis and inhibitory activity of Maillard reaction of 3,4-trans catechin and epicatechin dimers, procyanidin B1, B2, B3, B4 and their acetates

TMSOTf-catalyzed condensation of a potential electrophile with a nucleophile was achieved with a high level of 3,4-trans condensation, and we succeeded in the stereoselective synthesis of procyanidin B2 and its peracetate. Studies on the inhibitory activity of the Maillard reaction of four 3,4-trans series of catechin and epicatechin dimers, procyanidin B1, B2, B3 and B4, and their peracetates were also carried out.

Procyanidin B3 synthesis: a study of leaving group and Lewis acid activator effects upon interflavan bond formation

A range of electrophilic ethers were prepared via DDQ oxidation and alcoholic trapping (propanol, crotyl alcohol and propargyl alcohol) at the C4 position of (+)-catechin. The Lewis acid-mediated C4-substitution of each of these ethers was examined and it was found that the propargyl ether was the best overall electrophile. A range of Lewis acids were then examined as activators and it was found that BF3·OEt2 was the best in terms of both yield and stereochemical control at the C4 position. This newly developed set of conditions was then used to prepare the natural product nutraceutical procyanidin B3 with complete control of stereochemistry.

An efficient synthesis of procyanidins using equimolar condensation of catechin and/or epicatechin catalyzed by ytterbium triflate

Stereoselective synthesis of catechin and epicatechin dimers under intermolecular condensation of equimolar amount of catechin derivatives catalyzed by Yb(OTf)3. The coupled products were successfully converted to procyanidins B1, B2, B3, and B4, respectively. Procyanidins B1, B2, B3, and B4 could be used as standard compounds for identifying the polyphenols in natural source.

Synthesis of procyanidins by stepwise- and self-condensation using 3,4-cis-4-acetoxy-3-O-acetyl-4-dehydro-5,7,3′,4′-tetra-O-ben zyl-(+)-catechin and (-)-epicatechin as a key building monomer

3,4-cis-4-Acetoxy-3-O-acetyl-4-dehydro-5,7,3′,4′-tetra-O-ben zyl-(+)-catechin (1a) or (-)-epicatechin (1b) reacted high regio- and stereo-selectively with 1.5 equiv of the 5,7,3′,4′-tetra-O-benzyloxyflavan-3-ol (4a or 4b) in the presence of 1 equiv of TMSOTf to give the corresponding procyanidins. On the other hand, the self-condensation of 1a in the presence of a catalytic amount of B(C6F5)3 afforded wide-range procyanidins from dimer to 15-mer like a biomass.

Synthetic studies of proanthocyanidins. Highly stereoselective synthesis of the catechin dimer, procyanidin-B3.

A stereoselective synthesis of benzylated procyanidin-B3, a condensed catechin dimer, is described. Condensation of 5,7,3',4'-tetrabenzylcatechin with (2R,3S,4S)-5,7,3',4'-tetrabenzyloxy-3-acetoxy-4-methoxyflavan as an electrophile in the presence of TiCl4 led to octabenzylated procyanidin-B3 stereoselectively.

Synthetic studies of proanthocyanidins. Part 2: Stereoselective gram-scale synthesis of procyanidin-B3

A stereoselective synthesis of procyanidin-B3, a condensed catechin dimer, is described. Condensation of benzylated catechin with various 4-O-alkylated flavan-3,4-diol derivatives as an electrophile in the presence of a Lewis acid led to protected procyanidin-B3 and its diastereomer. In particular, the reaction using (2R,3S,4S)-3-acetoxy-5,7,3′,4′-tetrabenzyloxy-4-(2″- ethoxyethoxy)flavan as an electrophile in the presence of TMSOTf at -78°C afforded octa-O-benzylated procyanidin-B3 with high levels of stereoselectivity and in excellent isolation yields. Furthermore, we succeeded in a stereoselective gram-scale synthesis of protected procyanidin-B3.

Deuterium labeled procyanidin syntheses

Deuterium-labeled procyanidins have been prepared by hemisynthesis from taxifolin in order to investigate their metabolism in human. The structures of the desired deuterated natural compounds B3 10D (R1 = D, R2 = H) and B4 13D (R1 = D, R2 = H) were proven by spectroscopic and physical properties means, including 2H NMR spectrum. By-products with unatural absolute configuration at some centers were also formed along the process and were characterised.