Improved synthesis of structural analogues of (−)-epicatechin gallate for modulation of staphylococcal β-lactam resistance

Abstract

The high-yielding synthesis of enantiomerically pure epicatechin gallate analogues where the A and/or B-ring hydroxylation is reduced or altered has been achieved by optimising routes to the catechin stereochemistry. The B-ring analogues were synthesised by using an electrophilic ring closure onto an enantiomerically enriched epoxide as a key step. The A and B-ring hydroxyl-deleted analogues were synthesised through a Mitsunobu cyclisation. For the B-ring analogues, the anti- (catechin) stereochemistry was converted to the syn- (epicatechin) stereochemistry by a known oxidation/reduction protocol. Absolute stereochemistry was derived from either a Sharpless epoxidation or asymmetric dihydroxylation.

(‐)‐Epicatechin gallate, a metabolite of (‐)‐epigallocatechin gallate in grass carp, exhibits antiviral activity in vitro against grass carp reovirus

“…EGCG and ECG exhibit the highest similarity among the four substances above. ECG differs from EGCG only by the absence of one m ‐hydroxyl group (Anderson, Grounds, Reeves, & Taylor, ). While studying the pharmacokinetics of EGCG, we found that EGCG can be partially transformed into ECG in vivo.…”

Recent Advances in the Intramolecular Reactions of Epoxides with Arenes and Heteroarenes

“…As part of their efforts to synthesize structural analogues of (À)-epicatechin gallate for the modulation of staphylococcal b-lactam resistance, Anderson et al conducted the Friedel-Crafts EAC of enantiomerically pure anti-epoxyethers 33,p romoted by 1,1,3,3,3-hexafluoroisopropanol (HFIP), to obtain the cyclized products (34)i n3 3-46 %yield (Scheme 16). [22] Interestingly, syn-epoxyether 35 could not provide the desired product (36)u nder identical reaction conditions (Scheme 17). The authors attributed this failure to steric crowding between the aromatic ring and the methylene group of the epoxide in the reac-tive conformationt hat was required for the ring closure of compound 35.…”

Chiral Flavonoids as Antitumor Agents

“…Then, n-butylammonium fluoride (TBAF) was added to remove the silyl ether protecting (TBS) thus allowing the endo-cyclization reaction with camphorsulfonic acid (CSA) ment [159]. More recently, based on Sharpless asymmetric epoxidation, the synthesis of ( catechin gallate (ECG) (11) analogues was improved (Figure 21) [160]. The format enantiomeric pure epoxides with excellent enantiomeric excess was achieved from namoyl alcohol reaction with diethyl-L-tartrate, titanium isopropoxide and t-but droperoxide in dichloromethane.…”

“…Through reaction heating and the addition of hexafluoro-2-propanol ( they obtained catechin in good quantities, despite the fact that they could be improv extending the reaction time. The desired epicatechin stereochemistry was achieved idation with Dess-Martin periodinane followed by reduction with L-selectride [149 More recently, based on Sharpless asymmetric epoxidation, the synthesis of (−)epicatechin gallate (ECG) (11) analogues was improved (Figure 21) [160]. The formation of enantiomeric pure epoxides with excellent enantiomeric excess was achieved from cinnamoyl alcohol reaction with diethyl-L-tartrate, titanium isopropoxide and t-butyl hydroperoxide in dichloromethane.…”