Constrained saccharides: a review of structure, biology, and synthesis

Abstract

Review primarily covers from 1995-2018Carbohydrate function, recognized in a multitude of biological processes, provides a precedent for developing carbohydrate surrogates that mimic the structure and function of bioactive compounds. In order to constrain highly flexible oligosaccharides, synthetic tethering techniques like those exemplified by stapled peptides are utilized to varying degrees of success. Naturally occurring constrained carbohydrates, however, exist with noteworthy cytotoxic and chemosensitizing properties. This review highlights the structure, biology, and synthesis of this intriguing class of molecules.

Late-stage modification of bioactive compounds: Improving druggability through efficient molecular editing

“…Pharmaceutical chemists often perform SAR studies by introducing various substituents at specific positions of hit compounds using convergent synthetic routes. For instance, naturally occurring bioactive saccharides 405 and peptides 406 play vital roles in living cells and have potential therapeutic applications with subtle modification 407 , 408 . Chemists have made significant progress in selectively functionalizing the β -, γ -, and δ -positions of amino acids and short peptides using directing group strategies.…”

Late-stage modification of bioactive compounds: Improving druggability through efficient molecular editing

“…Pharmaceutical chemists often perform SAR studies by introducing various substituents at specific positions of hit compounds using convergent synthetic routes. For instance, naturally occurring bioactive saccharides 405 and peptides 406 play vital roles in living cells and have potential therapeutic applications with subtle modification 407 , 408 . Chemists have made significant progress in selectively functionalizing the β -, γ -, and δ -positions of amino acids and short peptides using directing group strategies.…”

Chemistry and biological activity of resin glycosides from Convolvulaceae species

“…The modified acyl groups are summarized in Figure 2, including short-chain aliphatic acids, for example, acetic (Ac), propionic (Pa), n-butyric (Ba), isobutyric (Iba), 2S-methylbutyric (Mba), 2R-methylbutyric (2R-Mba), 3-methylbutyric (3-Mba), angelic (Aga), tiglic (Tga), (2R,3R)-3-hydroxy-2-methylbutyric (nilic acid, Nla), (2S,3R)-3-hydroxy-2-methylbutyric (2S,3R-Nla), (2S,3S)-3-hydroxy-2-methylbutyric (2S,3S-Nla) and 3-hydroxy-2methylenebutyric (Hma) acids; long-chain fatty acids, for example, n-hexanoic (Hexa), n-octanoic (Octa), n-decanoic (Deca), n-dodecanoic (Dodeca), 10-methylundecanoic (Mundeca), 8R-hydroxy-dodecanoic (8R-Hydroxydodeca), n-tetradecanoic (Tetradeca), n-hexadecanoic (Hexadeca), n-octadecanoic (Octadeca), and neicosanoic (Eicosa); trans-cinnamic acid (Cna) and exogonic acid (Exg). 9,10,[35][36][37][38][39][40][41] There are also several monosaccharide acids which could acylate in the oligosaccharide core as modified residues and will be introduced in the following section.…”

“…The alkaline hydrolysis of the resin glycoside fraction of the Porana duclouxii afforded two glycosidic acids, poranic acids A and B (10 and 11). 51 The structure of poranic acid A (10) was elucidated as 11S-hydroxytetradecanoic acid…”

Total Synthesis of Starfish Cyclic Steroid Glycosides

“…The third subfamily, named steroidal cyclic glycosides, features a 16‐membered ring formed by bridging C3 and C6 of a 3β,6β‐dihydroxy‐Δ 7 ‐steroid with a trisaccharide via a glycosidic and a ether linkage, respectively (Figure 1a) [3–7] . Prominently, the cyclic structure consisting of a hybrid glycan and steroid scaffold and the ether bond tethering a glycan non‐reducing end to a steroid core stand out singular in the naturally occurring macrocyclic molecules [8, 9] …”

“…[3][4][5][6][7] Prominently, the cyclic structure consisting of a hybrid glycan and steroid scaffold and the ether bond tethering a glycan non-reducing end to a steroid core stand out singular in the naturally occurring macrocyclic molecules. [8,9] The prototypical cyclic starfish glycosides, namely luzonicoside A (1) and sepositoside A (3), were discovered in early 1980s by Minale and co-workers from Echinaster luzonicus and E. sepositus, respectively. [3,5] In 2015, Kicha et al re-investigated E. luzonicus collected from a different region and found another major cyclic saponin, named luzonicoside D (2).…”

Late-stage modification of bioactive compounds: Improving druggability through efficient molecular editing

“…Pharmaceutical chemists often perform SAR studies by introducing various substituents at specific positions of hit compounds using convergent synthetic routes. For instance, naturally occurring bioactive saccharides 405 and peptides 406 play vital roles in living cells and have potential therapeutic applications with subtle modification 407 , 408 . Chemists have made significant progress in selectively functionalizing the β -, γ -, and δ -positions of amino acids and short peptides using directing group strategies.…”

Chemistry and biological activity of resin glycosides from Convolvulaceae species

“…The modified acyl groups are summarized in Figure 2, including short-chain aliphatic acids, for example, acetic (Ac), propionic (Pa), n-butyric (Ba), isobutyric (Iba), 2S-methylbutyric (Mba), 2R-methylbutyric (2R-Mba), 3-methylbutyric (3-Mba), angelic (Aga), tiglic (Tga), (2R,3R)-3-hydroxy-2-methylbutyric (nilic acid, Nla), (2S,3R)-3-hydroxy-2-methylbutyric (2S,3R-Nla), (2S,3S)-3-hydroxy-2-methylbutyric (2S,3S-Nla) and 3-hydroxy-2methylenebutyric (Hma) acids; long-chain fatty acids, for example, n-hexanoic (Hexa), n-octanoic (Octa), n-decanoic (Deca), n-dodecanoic (Dodeca), 10-methylundecanoic (Mundeca), 8R-hydroxy-dodecanoic (8R-Hydroxydodeca), n-tetradecanoic (Tetradeca), n-hexadecanoic (Hexadeca), n-octadecanoic (Octadeca), and neicosanoic (Eicosa); trans-cinnamic acid (Cna) and exogonic acid (Exg). 9,10,[35][36][37][38][39][40][41] There are also several monosaccharide acids which could acylate in the oligosaccharide core as modified residues and will be introduced in the following section.…”

“…The alkaline hydrolysis of the resin glycoside fraction of the Porana duclouxii afforded two glycosidic acids, poranic acids A and B (10 and 11). 51 The structure of poranic acid A (10) was elucidated as 11S-hydroxytetradecanoic acid…”

Total Synthesis of Starfish Cyclic Steroid Glycosides

“…The third subfamily, named steroidal cyclic glycosides, features a 16‐membered ring formed by bridging C3 and C6 of a 3β,6β‐dihydroxy‐Δ 7 ‐steroid with a trisaccharide via a glycosidic and a ether linkage, respectively (Figure 1a) [3–7] . Prominently, the cyclic structure consisting of a hybrid glycan and steroid scaffold and the ether bond tethering a glycan non‐reducing end to a steroid core stand out singular in the naturally occurring macrocyclic molecules [8, 9] …”

“…[3][4][5][6][7] Prominently, the cyclic structure consisting of a hybrid glycan and steroid scaffold and the ether bond tethering a glycan non-reducing end to a steroid core stand out singular in the naturally occurring macrocyclic molecules. [8,9] The prototypical cyclic starfish glycosides, namely luzonicoside A (1) and sepositoside A (3), were discovered in early 1980s by Minale and co-workers from Echinaster luzonicus and E. sepositus, respectively. [3,5] In 2015, Kicha et al re-investigated E. luzonicus collected from a different region and found another major cyclic saponin, named luzonicoside D (2).…”

Late-stage modification of bioactive compounds: Improving druggability through efficient molecular editing

“…Pharmaceutical chemists often perform SAR studies by introducing various substituents at specific positions of hit compounds using convergent synthetic routes. For instance, naturally occurring bioactive saccharides 405 and peptides 406 play vital roles in living cells and have potential therapeutic applications with subtle modification 407 , 408 . Chemists have made significant progress in selectively functionalizing the β -, γ -, and δ -positions of amino acids and short peptides using directing group strategies.…”

Chemistry and biological activity of resin glycosides from Convolvulaceae species

“…The modified acyl groups are summarized in Figure 2, including short-chain aliphatic acids, for example, acetic (Ac), propionic (Pa), n-butyric (Ba), isobutyric (Iba), 2S-methylbutyric (Mba), 2R-methylbutyric (2R-Mba), 3-methylbutyric (3-Mba), angelic (Aga), tiglic (Tga), (2R,3R)-3-hydroxy-2-methylbutyric (nilic acid, Nla), (2S,3R)-3-hydroxy-2-methylbutyric (2S,3R-Nla), (2S,3S)-3-hydroxy-2-methylbutyric (2S,3S-Nla) and 3-hydroxy-2methylenebutyric (Hma) acids; long-chain fatty acids, for example, n-hexanoic (Hexa), n-octanoic (Octa), n-decanoic (Deca), n-dodecanoic (Dodeca), 10-methylundecanoic (Mundeca), 8R-hydroxy-dodecanoic (8R-Hydroxydodeca), n-tetradecanoic (Tetradeca), n-hexadecanoic (Hexadeca), n-octadecanoic (Octadeca), and neicosanoic (Eicosa); trans-cinnamic acid (Cna) and exogonic acid (Exg). 9,10,[35][36][37][38][39][40][41] There are also several monosaccharide acids which could acylate in the oligosaccharide core as modified residues and will be introduced in the following section.…”

“…The alkaline hydrolysis of the resin glycoside fraction of the Porana duclouxii afforded two glycosidic acids, poranic acids A and B (10 and 11). 51 The structure of poranic acid A (10) was elucidated as 11S-hydroxytetradecanoic acid…”

Total Synthesis of Starfish Cyclic Steroid Glycosides

“…The third subfamily, named steroidal cyclic glycosides, features a 16‐membered ring formed by bridging C3 and C6 of a 3β,6β‐dihydroxy‐Δ 7 ‐steroid with a trisaccharide via a glycosidic and a ether linkage, respectively (Figure 1a) [3–7] . Prominently, the cyclic structure consisting of a hybrid glycan and steroid scaffold and the ether bond tethering a glycan non‐reducing end to a steroid core stand out singular in the naturally occurring macrocyclic molecules [8, 9] …”

“…[3][4][5][6][7] Prominently, the cyclic structure consisting of a hybrid glycan and steroid scaffold and the ether bond tethering a glycan non-reducing end to a steroid core stand out singular in the naturally occurring macrocyclic molecules. [8,9] The prototypical cyclic starfish glycosides, namely luzonicoside A (1) and sepositoside A (3), were discovered in early 1980s by Minale and co-workers from Echinaster luzonicus and E. sepositus, respectively. [3,5] In 2015, Kicha et al re-investigated E. luzonicus collected from a different region and found another major cyclic saponin, named luzonicoside D (2).…”