Total Synthesis of Echinoside A, a Representative Triterpene Glycoside of Sea Cucumbers

Abstract

Echinoside A, a sulfonylated holostane tetrasaccharide with potent anticancer and antifungal activity, was synthesized in a longest linear sequence of 35 steps and 0.6 % overall yield. The synthetic approach is adaptable to the synthesis of congeners and analogues, as exemplified by the ready synthesis of ds-echinoside A and echinoside B, and thus will facilitate in-depth studies on the promising biological effects of echinoside A. Moreover, the present synthesis demonstrates the feasibility of synthetic access to the characteristic complex triterpene glycosides that occur ubiquitously in sea cucumbers.

Marine natural products

“…703 The total synthesis of the triterpene glycoside echinoside A has been reported, using an adaptable synthetic route that allowed preparation of desulfated echinoside A and the closely related echinoside B. 704 Surface plasmon resonance spectroscopy was used to assess the ability of starsh-derived lanosterol analogues to interact with human and fungal 14a-demethylase (CYP51). 705 Two examples, henricioside H and levisculoside G, were conrmed as modest inhibitors in a puried enzyme assay.…”

Progress in the Studies of Triterpene Glycosides From Sea Cucumbers (Holothuroidea, Echinodermata) Between 2017 and 2021

“…Interesting studies concerning the total chemical synthesis of sea cucumber glycosides are also known. 14,15…”

Synthesis of Sea Cucumber Saponins with Antitumor Activities

“…23 Glycosylation of 18 with trisaccharide donor 19 12 under the catalysis of Ph 3 PAuOTf (0.3 equiv) in CH 2 Cl 2 at rt afforded β-tetrasaccharide 20 in a satisfactory 90% yield. Then, reduction of the 12-carbonyl group with NaBH 4 afforded the 12α-OH derivative; 12 subsequent acetylation of the 12-OH and removal of the 24-O-TBS group with a hydrogen fluoride (HF)• pyridine complex in MeOH provided 21 (52% for three steps). The dehydration of the 24-hydroxy group should be regioselective, and Dolle et al have disclosed that Martin sulfurane was effective for the conversion of 24-OH to Δ 24(25) double bond in sterol substrates.…”

“…12 The synthesis of echinoside A (1) required 63 steps from readily available materials, including lanosterol, glucose, and xylose. 12 Pervicoside C (3) is a simpler congener of echinoside A (1) in the absence of the α-hydroxy group at C17. Pervicoside C (3) and its Δ 24(25) congener, namely, pervicoside B (2), were originally characterized in their desulfonated forms from sea cucumber Holothuria pervicax.…”