Synthesis of Kaempferol 3-O-(3′′,6′′-Di-O-E-p-coumaroyl)-β-d-glucopyranoside, Efficient Glycosylation of Flavonol 3-OH with Glycosyl o-Alkynylbenzoates as Donors

Abstract

Kaempferol 3-O-(3'',6''-di-O-E-p-coumaroyl)-β-D-glucopyranoside (1), an optimal metabolite of Scots pine seedlings for protection of deep-lying tissue against damaging UV-B, represents a typical acylated flavonol 3-O-glycoside. This compound was synthesized for the first time via two approaches. The first approach, starting with kaempferol, featured formation of the flavonol 3-O-glycosidic linkage with a glycosyl bromide under conventional PTC conditions. In the second approach, 5,7,4'-tri-O-benzyl-kaempferol was readily prepared from 2',4',6'-trihydroxyacetophenone and p-hydroxybenzoic acid, which was coupled with a glucopyranosyl o-hexynylbenzoate under the catalysis of a gold(I) complex to provide the desired 3-O-glycoside in excellent yield. A variety of the glycosyl o-hexanylbenzoates equipped with the 2-O-benzoyl group were also proven to be highly efficient donors for construction of the flavonol 3-O-glycosidic linkages.

Recent Advances in Transition Metal-Catalyzed Glycosylation

“…93 Additionally, it has been applied in the synthesis of kaempferol glycoconjugates, 94,95 ginsenosides, 96 and the chemoselective glycosylation of carboxylic acids. 97 The method is amenable to N -glycosylation strategies, which was demonstrated with the synthesis of purine and pyrimidine nucleobases.…”

Efficient synthesis of baicalin and its analogs

“…Retrosynthetic analysis of baicalin 1 is shown in Scheme 1. The target molecule could be obtained from fully Here, 6-OTBDPS protected glucosyl bromide 4 was chosen as the donor due to two reasons: First, donor equipped with silyl group could have a higher reactivity than peracylated glycuronic donors, which is the prerequisite for high-yielding glycosylation; 15 Second, glycosyl bromides are the first type of donor applied in flavonoid glycosides synthesis, 16 and three protocols, including Koenigs-Knorr protocol, Zemplen-Farkas protocol, and PTC protocol, have been developed concerning these donors. 17 Acceptor 5 can be traced back to baicalein 2, which could be synthesized from cheap starting material as reported previously.…”

Glycosylation via Transition‐Metal Catalysis: Challenges and Opportunities

“…This gold(I)‐catalyzed glycosylation using glycosyl ortho ‐alkynylbenzoates as donors was later successfully applied to the synthesis of a number of O ‐linked glycosides and glycoconjugates, such as β‐ N ‐acetylglucosaminidases inhibitor TMG‐chitotriomycin, cyclic triterpene saponin, kaempferol 3‐ O ‐(3′′,6′′‐di‐ O ‐ E ‐ p ‐coumaroyl)‐β‐ d ‐glucopyranoside, nucleoside, ginsenoside Rh2 and chikusetsusaponin‐LT8, kaempferol 3‐ O ‐(3′′,6′′‐di‐ O ‐ E ‐ p ‐coumaroyl)‐α‐ l ‐rhamnopyranosides, lupane‐type saponins, digitoxin, kaempferol 3,7‐ O ‐bisglycosides, saponin P57, N – O linked saccharides, Starfish Saponin Goniopectenoside B, diverse ginsenosides, Nucleoside Antibiotic A201A, Linckosides A and B, astrosterioside A, Tunicamycins, immunosuppressant periploside A…”