Efficient Synthesis of the Deoxysugar Part of Versipelostatin by Direct and Stereoselective Glycosylation and Revision of the Structure of the Trisaccharide Unit

Abstract

Efficient synthesis of the deoxysugar part of versipelostatin (VST) was achieved by direct and stereoselective glycosylation of the reduced VST aglycon. Activation of 2-deoxyglycosyl imidate with IBr under basic conditions enables alpha-selective glycosylation of beta-2-deoxylglycosides without anomerization. Comparison of the synthetic and natural VST products using NMR indicates that versipelostatin has a beta-D-digitoxose-(1,4)-alpha-L-oleandrose-(1,4)-beta-D-digitoxose trisaccharide. In addition, results of a biological assay indicate that the deoxyoligosaccharide unit of the synthetic glycoside was important for biological activity of the compound.

Spirotetronate Polyketides as Leads in Drug Discovery

“…71b In addition to these studies, Takahashi et al demonstrated the importance of the l -oleandrose sugar for the bioactivity, and changes in the oxidation state of C-7 had no effect on biological activity. 72 …”

Stereoselective Formation of 2‐Deoxyglycosidic Bonds in Biologically Active Natural Products

“…[18][19][20] As shown in Scheme 38.9, treatment of the 4-O-benzylsulfonylolivosyl imidate 21 and 23 with I 2 and a catalytic amount of triethylsilane in toluene at À94 C provided the 2-deoxy-b-glycoside 24 in 94% yield with a nearly complete b selectivity (a/b ¼ 5/>95). [18][19][20] As shown in Scheme 38.9, treatment of the 4-O-benzylsulfonylolivosyl imidate 21 and 23 with I 2 and a catalytic amount of triethylsilane in toluene at À94 C provided the 2-deoxy-b-glycoside 24 in 94% yield with a nearly complete b selectivity (a/b ¼ 5/>95).…”

Synthesis and Biological Evaluation of O‐Methylated Glycolipids Related to PGLs via Direct Stereoselective Glycosidation and Sequential Suzuki–Miyaura Coupling using Boracyclane

“…Obviously, the required modification step after construction of the sugar chain would increase the number of synthetic steps, and these would not be adaptable to the synthesis of 2‐ O ‐methyl‐α‐fucosides possessing an equatorial‐orientated C2 oxygen functional group. On the other hand, we had previously reported an efficient synthesis of 2‐deoxy‐α‐glycosides via the glycosidation of 2‐deoxyglycosyl imidates with IBr and n Bu 4 NBr under basic conditions . We further speculated that this method could involve a S N 2‐like substitution of in situ‐generated and unstable β‐glycosyl halides with glycosyl acceptors that could provide the 2‐deoxy‐α‐glycosides, which would make it adaptable to the direct synthesis of 2‐ O ‐methyl‐α‐glycosides.…”

“…On the other hand, we had previously reported an efficient synthesis of 2-deoxy-a-glycosides via the glycosidation of 2-deoxyglycosyl imidates with IBr and nBu 4 NBr under basic conditions. [12] We further speculated that this method could involve aS N 2-like substitution of in situ-generated and unstable b-glycosyl halides with glycosyla cceptors that could provide the 2-deoxy-a-glycosides,w hich would make it adaptable to the direct synthesis of 2-O-methyl-a-glycosides. Herein, we report the preparation of PGL-1 and PGL-tb1 containing 4-bromophenyl glycosides by direct a-selective glycosidation of 2-O-methyl-glycosyl imidates and modification of the glycosides by sequential Suzuki-Miyaura palladium-catalyzedc ross-cou-pling using ab oracyclane.…”