First Total Synthesis of 5′-O-α-d-Glucopyranosyl Tubercidin

Abstract

The first total synthesis of 5′-O-α-d-glucopyranosyl tubercidin was successfully developed. It is a structurally unique disaccharide 7-deazapurine nucleoside exhibiting fungicidal activity, and was isolated from blue-green algae. The total synthesis was accomplished in eight steps with 27% overall yield from commercially available 1-O-acetyl-2,3,5-tri-O-benzoyl-β-d-ribose. The key step involves stereoselective α-O-glycosylation of the corresponding 7-bromo-6-chloro-2′,3′-O-isopropylidene-β-d-tubercidin with 2,3,4,6-tetra-O-benzyl-glucopyranosyl trichloroacetimidate. All spectra are in accordance with the reported data for natural 5′-O-α-d-glucopyranosyl tubercidin. Meanwhile, 5′-O-β-d-glucopyranosyl tubercidin was also prepared using the same strategy.

Marine natural products

“…The first total syntheses of 19 cyanobacteria-derived compounds were reported during 2020, including ambigols A–E, 123 biseokeaniamides A–C, 124 5′- O -α- d -glucopyranosyl tubercidin, 125 kakeromamide A, 126 anaephenes A and B, 127 lyngbyoic acid, 128 anaenamides A 273 and B 274 , 110 and anaenoic acid 275 , 110 biselyngbyolide C, 129 tutuilamide A 262 , 130 and kasumigamide 307 . 131 The synthesis of several kasumigamide stereoisomers enabled the structure revision of this MNP.…”

Discovery of 3′-O-β-Glucosyltubercidin and the Nucleoside Specific Glycosyltransferase AvpGT through Genome Mining

“…Pure chemical synthesis of glycosyl derivatives of nucleosides with regio-and stereocontrol is a non-trivial undertaking; for example, synthesis of 3′-O-β-glucosyl adenosine by Feng and co-workers required 11 steps, 21 while synthesis of 5′-O-α-glucopyranosyl tubercidin by Ouyang and co-workers required 15 steps. 23 The complexity arises primarily from the numerous protection and deprotection steps involving the glucose, ribose, and purine moieties which are necessary to control glycosidic bond formation. In contrast, the preliminary substrate screen explored in this work shows that AvpGT can directly glucosylate the 3′-hydroxyl of five different purine nucleosides and is active with two different glycosyl donors.…”

“…A total synthesis of 5′-O-α-glucopyranosyl tubercidin has been recently published. 23 Of these examples, only one glycosyltransferase (GT) responsible for the modification has been identified. In the case of nucleocidin 2b, glucosylation is performed by the inverting GT NucGT.…”

“…This subfamily includes 5′- O -α-glucosyl tubercidin and 5′- O -α-glucosyl toyocamycin from Plectonema radiosum and Tolypothrix tenuis, respectively; 3′- O -α-glucosyl inosine from the crustacean Ligia exotica; and more recently, 3′- O -β-glucosyl-4′-fluoroadenosine 2c , 3′- O -β-glucosyl nucleocidin 2d , 3′- O -β-glucosyl adenosine, and 3′- O -β-glucosyl-5′- O -sulfamyl adenosine from Streptomyces calvus (Figure ). A total synthesis of 5′- O -α-glucopyranosyl tubercidin has been recently published . Of these examples, only one glycosyltransferase (GT) responsible for the modification has been identified.…”

Synthesis of Marine Natural Products and Molecules Inspired by Marine Substances

“…Ouyang et al described the first eight steps of the total synthesis of 5 -O-α-D-Glucopyranosyl Tubercidin, a disaccharide 7-deazapurine nucleoside characterized by fungicidal activity [9]. The chemical approach, based on trichloroacetimidate strategy, consisted in one-pot Vorbrüggen glycosylation of protected ribose with 6-chloro-7-bromo-7deazapurine and stereoselective α-O-glycosylation of 7-deazapurine nucleoside derivative with 2,3,4,6-tetra-O-benzyl-glucopyranosyl trichloroacetimidate.…”