Concise first total synthesis of phenylethanoid glycosides parvifloroside A and crassifolioside

Abstract

The first total synthesis of phenylethanoid glycosides parvifloroside A 1 and crassifolioside 2 is disclosed, achieving excellent 31 % and 33 % overall yield, respectively. The synthesis exploited the inherent reactivity differences among the free hydroxyl groups on 4-O-caffeoyl glucopyranoside 3 intermediate, enabling regioselective caffeoylation and rhamnosylation. The key to the synthesis is using chiral 4-pyrrolidinopyridine organocatalyst 6 to achieve the regioselective caffeoylation and migration of acyl groups. Notably, the synthesis avoids the common challenge of E:Z isomerization of the caffeoyl moiety's double bond. Additionally, only a single protection/deprotection step is employed, significantly simplifying the process. This concise approach provides a practical route to these natural products and establishes a versatile strategy for synthesizing a wide array of phenylethanoid glycosides with similar substitution patterns.