Revised Structures of Gambiriins A1, A2, B1, and B2, Chalcane-Flavan Dimers from Gambir (Uncaria gambir Extract)

Abstract

Gambir, an official pharmacopoeic medicine in Japan, is the aqueous extract of the leaves and young twigs of Uncaria gambir ROXB. (Rubiaceae).2) The extract has been used for the treatment of diarrhea and sore throat as an astringent medicine in Southeast Asia, 3) and also for hoarseness, as an ingredient of the kampo medicine "Kyoseihatekigan."Flavan monomers, (ϩ)-catechin (1) and (ϩ)-epicatechin (2), 4) several other dimeric compounds 5) related to 1, as well as alkaloids, 6,7) have been reported to be the constituents. Our investigation on the polyphenolic contents of a manufactured gambir product led to the isolation of 1, 2, and seven dimeric flavans 3-9. Although the seven dimeric flavans were known compounds, the present study revealed that the stereostructures of four of the chalcane-flavan dimers should be revised to 6-9. Their 1 H-and 13 C-NMR spectral assignments are also shown here, since those were not reported in detail previously. 5,8) Results and DiscussionA manufactured product of gambir purchased in Japan was extracted with MeOH, and the extract was fractionated by column chromatography on Dia-ion HP-20 using aqueous MeOH. (ϩ)-Catechin (1) was crystallized from the eluate with 20% MeOH, and the mother liquor was subjected to column chromatography on a Toyopearl HW-40 to give a fraction containing both monomeric and dimeric flavans. The fraction was further chromatographed on octadecylsilyl (ODS) silica gel, Sephadex LH-20, and MCI-gel CHP-20P columns to give (ϩ)-catechin (1), (ϩ)-epicatechin (2), procyanidin B1 (3), 9,10) procyanidin B3 (4), 11) gambiriin C (5), 5) and gambiriin A1 (6). The eluate, with 40% MeOH from the column of Dia-ion HP-20, was separated in an analogous way to give gambiriin A2 (7), gambiriin B1 (8), and gambiriin B2 (9). Gambiriin A1 (6) was obtained as an amorphous powder. The dimeric molecular formula, C 30 H 28 O 12 , was indicated by the [MϩH] ϩ ion peak at m/z 581 in the electrospray-ionization (ESI)-MS. The showed a large coupling constant (7.5 Hz), indicating that the lower unit was 2,3-trans catechin. The 2,3-trans structure was also validated by the 13 C-NMR spectrum, which showed the C-2 L signal at d 82.5. The remaining set of the methine-methine-methylene protons [d: 2.56 (H-ga U ), 2.95 (Hgb U ), 4.68 (H-b U ), 4.75 (H-a U )] was attributable to the substituted propyl group in the chalcane structure. The molecular formula of 6, which was indicated by the ESI-MS, also substantiates this open-chain chalcane structure.The rotating frame nuclear Overhauser effect spectroscopy (ROESY) of 6 showed correlations of H-a U /H-2Ј L and Hb U /H-2Ј L , indicating the presence of an interflavonoid link between position C-8 L and the upper chalcane unit (C-a U ) (Fig. 2). These correlations would not be observed if the linkage occurred at C-6 L . The aliphatic protons of 6 appeared as broad signals, due to the restricted rotation around the interflavonoid linkage, which confirmed the location of the linkage at C-8 L .The assigned structure of 6 based on these data suggest...

Secondary Metabolites from Rubiaceae Species

“…Uncaria gambir Proanthocyanidins: gambiriins A1-A2 ; gambiriins B1-B2; (+)-catechin; (+)-epicatechin; procyanidin B1; procyanidin B3; gambiriin [146] Uncaria glabrata Monoterpene indole alkaloids: 14α-hydroxyrauniticine; rauniticine; uncarine C-E; glabratine; deoxycordifoline [147] Indole alkaloid: ajmalicine Oxindole alkaloids: formosanine or uncarine B; isomitraphylline; mitraphylline [148] Triterpenes: Triterpenes: oleanolic acid; 3β,6β,19α-trihydroxyurs-12-en-28-oic acid [170] Triterpenes: 3β,6β,19α-trihydroxyurs-12-en-23-al-28-oic acid; 3β,19α-dihydroxy-6-oxo-urs-12-en-23-al-28-oic acid; 3β,19α-dihydroxy-6-oxo-urs-12-en-23-ol-28-oic acid [171] Triterpene: 23-nor-24-esomethylene-3β,6β-19α-trihydroxyurs-12-en-28 oic acid; 3β,6β,19α-trihydroxyurs-12-en-28-oic acid; 3-oxo-6β,19α-dihydroxyurs-12-en-28 oic acid; oleanic acid [192] Triterpenes: pomolic acid methyl ester; ursolic acid methyl ester; oleanolic acid methyl ester [193] Alibertia sessilis…”

Tannins and Catechins Content of Gambier (Uncaria Gambier Roxb) in Relation With Adhesive Qualities and Bonding Strength of Cold Setting Glue.

“…In research the content of catechins ranged from 14.76% to 54.97%. The results of Taniguchi et al (2007) found that from 31 gambier samples collected from gambier traders in 4 countries, Japan, Indonesia, Singapore, and China, it was known that catechin content ranged from 0.17 g to 0.76 g per 1 g sample with the average of 0.43g / g or 43%.…”

On the probable composition of ‘Jamaican stone’ aphrodisiac

“…Gambir is mainly composed of cattechu-tanic acid (a tannin), (+)-catechin (see Figure 2), (+)epicatechin, dimeric proanthocyanidins, procyanidins B1 and B3, and gambiriins A1, A2, B1, B2 and C (Taniguchi et al, 2007), much of them 3´,4´,5,7-tetrahydroxysubstituted derivatives of 3,4dihydro-2-phenyl-2H-1-benzopyran.…”