The First Total Synthesis of Praecoxin B and Pterocarinin C, Two Natural Products of the Tannin Class

Abstract

Enantiomerically pure diphenic ester 3 was obtained by a-and p-anomers (7 (4:l). The natural product praecoxin B esterification of acyl chloride 2 with the glucose derivative 1 (8) was obtained by hydrogenative debenzylation. A second by kinetic resolution. Hydrolysis of the ester 3, acylation of member of the ellagitannin group pterocarinin C (11) was the free OH groups at C-4 and C-6 of the diol4 with acid 5 obtained from the common intermediate 7 by acylation in the followed by irradiation led to the anomerically deprotected anomeric position to 10 followed by debenzylation.Praecoxin B and pterocarinin C (11) [4,5] are members of the large class of glycosidic natural products from vegetable extracts known as ellagitannin~[~.~j. At present, over 500 structurally characterized ellagitannins are identified[*]. These plant polyphenols are commercially used in the leather and wine industryL6] as well as in the traditional herbal Therefore much attention was focused on the development of general approaches to the compounds of this c l a~s [~-'~] in the past years (for a reviewwe reported about the synthesis of the ellagitannin ~trictinin['~~'~] using a stereoselective esterification reaction. The successful kinetic resolution (see below) of racemic biaryls prompted us to investigate the synthesis of the natural products praecoxin B and pterocarinin C (11) [4,5] in enantiomerically pure form employing a similar strategy. Now we report about the total synthesis of 8 and 11 starting from racemic diphenic acid chloride 2[17] and the glucoside derivative (l)[1s319]. We used a modified method of Steglich for esterification reactions[l61 to produce diester 3 in a diastereoselective manner. The use of an excess of 4-(dimethy1amino)pyridine (DMAP) (three equivalents) accelerated the esterification to give diester 3 in 38% yield with respect to the sugar component 1 corresponding to a 76% theoretical yield. 'H and I3C NMR-data of diester 3 unambiguously show the purity of this diastereomer (de > 97%), followed by the absence of the corresponding isomer. To determine the absolute configuration of this stereoisomer, the diester 3 was subjected to hydrolysis using anhydrous potassium hydroxide prepared from potassium tert-butoxide and a trace of water in THF as proposed by Gassman ["]. An optically pure (5')-hexabenzyloxydiphenic acid was obtained from this reaction as shown by comparison of its specific rotation with that reported for (S)-atropi~omer['~l. Thus, the absolute configuration of the observed stereoisomeq' 3 was unam- In a preceedingI biguously determined to be (S). We also obtained a polar fraction which has not yet been fully characterized, but it is assumed to be most probably disacharide of (R)-diphenic acid [21]. Treatment of diester 3 with 2 N HCI in THF then gave the diol4 in 91% yield as a yellow crystalline material. The diol 4 was acylated with acid 5[223231 in the presence of 1,3-dicyclohexylcarbodiimide (DCC) and DMAP to afford the digalloylated compound 6 in 78% yield with respect to the diol compone...

Total Synthesis of Ellagitannins <i>via</i> Sequential Site-Selective Functionalization of Unprotected D-Glucose

“…The overall steps for the chemical total syntheses are much shorter than those reported based on the conventional synthetic strategy. 15,26) It is worthy to note that the key player in our chemical synthesis, organocatalyst 9 with molecular weight of only 833, can effectively perform the site-selective introduction of the requisite galloyl group at the desired site, resulting in overall synthetic efficiency comparable with the biosynthetic pathway promoted by several enzymes with huge molecular weights. The advantages of chemical synthesis of naturally occurring bioactive compounds involve easier derivatization, definite structure-determination, and large-scale synthesis.…”

The First Total Syntheses of Enantiomerically Pure Naturally Occuring Ellagitannins Gemin D and its Regioisomer Hippomanin A

“…The acylation reaction of both regioisomers 11 and 12 with the benzyl-protected gallic acid 17 [26] in the presence of 4-(dimethylamino)pyridine (DMAP) and 1,3-dicyclohexylcarbodiimide (DCC) afforded a mixture of the monoacylated compounds 18 and 19, respectively (Scheme 1).…”

“…The esterification reaction of the racemic hexabenzyloxydiphenic acid (21) [26] with diols 20 and 23 proceeded diastereoselectively to produce both diastereoisomers 22 and 24, respectively. The absolut configuration of the obtained diastereoisomers 22 and 24 were determined to be (S) after completion of the syntheses of both naturally occuring ellagitannins gemin D (1) and hippomanin A (2) by hydrogenolysis of the benzyl groups of the diastereoisomers 22 and 24.…”

Plant Polyphenols: Chemical Properties, Biological Activities, and Synthesis

“…relied on (nonbiomimetic) route B using perbenzylated HHDP units, either racemic or atropisomerically pure. They achieved the total synthesis of the 4,6‐( S )‐HHDP‐bearing ellagitannins strictinin,157a gemin D and its regioisomer hippomanin A,157b the natural 1,3‐di‐ O ‐galloyl‐4,6‐ O ‐( S )‐hexahydroxydiphenoyl‐β‐ D ‐glucopyranoside ( 27 ),157c as well as the 2,3‐( S )‐HHDP‐containing praecoxin B and pterocaryarin C157d (Figure 22). Khanbabaee et al.…”