Efficient Preparation of 2‐SAc‐Glycosyl Donors and Investigation of Their Application in the Synthesis of 2‐Deoxyglycosides

Abstract

In this study, we have developed efficient strategies for the synthesis of glycosyl donors with 2-thioacetyl (SAc) groups in order to synthesize 2-deoxysugars with exclusive α/β-configuration. Starting from free methyl glycosides, four methyl 2-SAc glycosides were synthesized with high efficiency mainly through the double serial inversion strategy, and further turned into four corresponding 1-OAc, 2-SAc α-glycosyl donors (manno-, gluco-, galacto-and talo-types) and four corresponding 1-STol, 2-SAc 1,2-cis-glycosyl donors (manno-, gluco-, galacto-and talo-types). Glycosylation of the 1-OAc, 2-SAc donors and further 2-deoxysugar synthesis have also been investigated in this study.

Visible-Light-Promoted Desulfurization to Synthesize Deoxyglycosides

“…Notably, 2-deoxyglycosides 39 and 42 containing benzyl protecting groups were isolated in 89 and 85% yields, respectively. In comparison with this, the UV-light-promoted desulfurization failed to yield pure 39 due to unknown inseparable side products. This further confirms that this visible-light-promoted desulfurization can indeed reduce side reactions that often occur in UV-promoted desulfurization processes.…”

“…In the end, we applied this visible-light-promoted desulfurization to the synthesis of 2-deoxyglycosides with exclusive α-stereoselectivity (Figure ). Glycosylation of 1-OAc, 2-SAc 1, and 2- trans -α-glycosyl donors with acceptors led to products with exclusive α-configuration, , and then 2-deoxyglycoside derivatives 31 – 42 with exclusive α-configuration were efficiently obtained in 70–89% yields by this one-pot desulfurization method. Notably, 2-deoxyglycosides 39 and 42 containing benzyl protecting groups were isolated in 89 and 85% yields, respectively.…”

“…The crude material was purified by flash column chromatography (ethyl acetate/petroleum ether = 1:3), which afforded 40 as a colorless oil (71.5 mg, 86% yield); 1 (41). 33 Methyl 2,3,4-tri-Obenzoyl-6-O-(2-S-acetyl-3,4,6-tri-O-acetyl-2-thio-α-D-talopyranosyl)α-D-glucopyranoside 41′ was synthesized in light of the reported literature. 33 Following procedure A, 41' (173.0 mg, 0.2 mmol) in DMF (1.0 mL) was allowed to react with hydrated hydrazine (17.7 μL, 0.36 mmol) for 3 min, followed by the addition of TCEP•HCl (145 mg, 0.5 mmol) and Ru(bpy) 3 Cl 2 (3.0 mg, 0.004 mmol).…”

“…33 Methyl 2,3,4-tri-Obenzoyl-6-O-(2-S-acetyl-3,4,6-tri-O-acetyl-2-thio-α-D-talopyranosyl)α-D-glucopyranoside 41′ was synthesized in light of the reported literature. 33 Following procedure A, 41' (173.0 mg, 0.2 mmol) in DMF (1.0 mL) was allowed to react with hydrated hydrazine (17.7 μL, 0.36 mmol) for 3 min, followed by the addition of TCEP•HCl (145 mg, 0.5 mmol) and Ru(bpy) 3 Cl 2 (3.0 mg, 0.004 mmol). The crude material was purified by flash column chromatography (ethyl acetate/petroleum ether = 1:3), which afforded 41 as a colorless oil (134 mg, 85% yield); 1 H NMR (400 MHz, CDCl 3 ): δ 8.05−7.85 (m, 6 H), 7.59−7.29 (m, 9 H), 6.17 (t, J = 9.7 Hz, 1 H), 5.65 (t, J = 9.9 Hz, 1 H), 5.…”

“…For example, under UV irradiation, desulfurization of per-acetylated glycosyl 1-thiols may produce acetyl migration byproducts caused by β-(acyloxy)alkyl radical rearrangement, 30,37,38 and desulfurization of substrates containing benzyl-type protecting groups may also produce unknown byproducts. 33,39 A reaction under visible-light irradiation is usually milder, in which a photocatalyst has to be employed to transfer energy from the light to the substrate. 40−44 The desulfurization of cysteinyl peptide under visible light has been reported by Guo's group for the synthesis of peptides through the ligation-desulfurization protocol.…”