A practical, efficient large-scale synthesis of 1,6-anhydrohexopyranoses

Zottola, Mark A.; Alonso, Ricardo; Vite, Gregory D.; Fraser‐Reid, Bert

doi:10.1021/jo00287a029

Cited by 69 publications

(21 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…O -Benzylation [ 40 ] of 14 followed by azidolysis [ 41 ] furnished 15 . 2-Azido-3,4-epoxide 18 was prepared from readily available [ 42 ] 2,3-isopropylidene-D-mannosan ( 16 ) in five steps ( Scheme 2 ). Tosylation of 16 [ 43 ], followed by hydrolysis of the benzylidene acetal [ 44 ] and oxirane ring closure [ 45 ] at C-4 delivered 1,6:3,4-dianhydro derivative 17 .…”

Section: Resultsmentioning

confidence: 99%

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

Horník¹,

Šťastná²,

Cuřínová³

et al. 2016

Beilstein J. Org. Chem.

View full text Add to dashboard Cite

Summary Background: Derivatives of D-glucosamine and D-galactosamine represent an important family of the cell surface glycan components and their fluorinated analogs found use as metabolic inhibitors of complex glycan biosynthesis, or as probes for the study of protein–carbohydrate interactions. This work is focused on the synthesis of acetylated 3-deoxy-3-fluoro, 4-deoxy-4-fluoro and 3,4-dideoxy-3,4-difluoro analogs of D-glucosamine and D-galactosamine via 1,6-anhydrohexopyranose chemistry. Moreover, the cytotoxicity of the target compounds towards selected cancer cells is determined. Results: Introduction of fluorine at C-3 was achieved by the reaction of 1,6-anhydro-2-azido-2-deoxy-4-O-benzyl-β-D-glucopyranose or its 4-fluoro analog with DAST. The retention of configuration in this reaction is discussed. Fluorine at C-4 was installed by the reaction of 1,6:2,3-dianhydro-β-D-talopyranose with DAST, or by fluoridolysis of 1,6:3,4-dianhydro-2-azido-β-D-galactopyranose with KHF2. The amino group was introduced and masked as an azide in the synthesis. The 1-O-deacetylated 3-fluoro and 4-fluoro analogs of acetylated D-galactosamine inhibited proliferation of the human prostate cancer cell line PC-3 more than cisplatin and 5-fluorouracil (IC50 28 ± 3 μM and 54 ± 5 μM, respectively). Conclusion: A complete series of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine is now accessible by 1,6-anhydrohexopyranose chemistry. Intermediate fluorinated 1,6-anhydro-2-azido-hexopyranoses have potential as synthons in oligosaccharide assembly.

show abstract

Section: Resultsmentioning

confidence: 99%

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

Horník¹,

Šťastná²,

Cuřínová³

et al. 2016

Beilstein J. Org. Chem.

View full text Add to dashboard Cite

show abstract

“…The alcohol 177 , obtained by ketalization of l -sorbose ( 157 ) was oxidised with pyridinium chlorochromate (PCC) to give the ketone 178 [ 85 ] ( Scheme 42 ). The organocatalyst 182 was synthesised from d -mannose by regioselective tosylation and intramolecular nucleophilic substitution to afford the 1,6-anhydrosugar 181 [ 97 ] . Subsequent ketalization and oxidation allowed the formation of 182 ( Scheme 42 ).…”

Section: Sugar Ketonesmentioning

confidence: 99%

Synthesis and Applications of Carbohydrate-Based Organocatalysts

et al. 2021

View full text Add to dashboard Cite

Organocatalysis is a very useful tool for the asymmetric synthesis of biologically or pharmacologically active compounds because it avoids the use of noxious metals, which are difficult to eliminate from the target products. Moreover, in many cases, the organocatalysed reactions can be performed in benign solvents and do not require anhydrous conditions. It is well-known that most of the above-mentioned reactions are promoted by a simple aminoacid, l-proline, or, to a lesser extent, by the more complex cinchona alkaloids. However, during the past three decades, other enantiopure natural compounds, the carbohydrates, have been employed as organocatalysts. In the present exhaustive review, the detailed preparation of all the sugar-based organocatalysts as well as their catalytic properties are described.

show abstract

“…A process for obtaining enantiomerically pure β-D-1,3-dioxolane nucleosides via a stereospecific synthesis has also been reported (Scheme 1 ). The fourteen-step synthesis of (−)-DAPD from 1,6-anhydro-D-mannose 11 resulted in a modest overall yield. It involved a difficult and low yielding Pb(OAc) 4 oxidation to dioxolane acetate, 1 12 and multiple chromatography purification steps that make the process unsuitable for commercial development.…”

Section: Introductionmentioning

confidence: 99%

Scaleable processes for the synthesis of (−)-β-d-2,6-diaminopurine dioxolane (Amdoxovir, DAPD) and (−)-β-d-2-aminopurine dioxolane (APD)

Zhou¹,

Coats²,

Zhang³

et al. 2012

Tetrahedron

View full text Add to dashboard Cite

An efficient and scalable synthesis of (−)-DAPD and (−)-APD has been developed. We discovered that t-butyl cyanoacetate can be used as a new additive for the sugar nucleoside base coupling step en route to DAPD with improved β-selectivity and an isolated yield four fold greater than the original process scale method. Using this new process, (−)-DAPD has been prepared on greater than 20 g scale. In the synthesis of (−)-APD, a key enzyme-catalyzed hydrolysis reaction afforded the water-soluble deprotected α-anomer while leaving the β-anomer completely untouched.

show abstract

A practical, efficient large-scale synthesis of 1,6-anhydrohexopyranoses

Cited by 69 publications

References 1 publication

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

Synthesis and Applications of Carbohydrate-Based Organocatalysts

Scaleable processes for the synthesis of (−)-β-d-2,6-diaminopurine dioxolane (Amdoxovir, DAPD) and (−)-β-d-2-aminopurine dioxolane (APD)

Contact Info

Product

Resources

About