Co-reporter:Dina Lloyd, Marissa Bylsma, Danielle K. Bright, Xizhao Chen, and Clay S. Bennett
The Journal of Organic Chemistry April 7, 2017 Volume 82(Issue 7) pp:3926-3926
Publication Date(Web):March 10, 2017
DOI:10.1021/acs.joc.7b00065
The use of a combination of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and β-pinene permits the removal of 2-naphthylmethyl (Nap) ether protecting groups on highly sensitive substrates. The reaction tolerates both acid and base sensitive protecting groups, and products are afforded in 68–96% yield. The utility of the method is demonstrated by the removal of the Nap protecting groups on highly sensitive 2,6-dideoxy-sugar disaccharides.
Co-reporter:Dr. Jason M. Nogueira;Marissa Bylsma;Danielle K. Bright ; Clay S. Bennett
Angewandte Chemie International Edition 2016 Volume 55( Issue 34) pp:10088-10092
Publication Date(Web):
DOI:10.1002/anie.201605091
Abstract
We have found that activating either 2,3-bis(2,3,4-trimethoxyphenyl)cyclopropenone or 2,3-bis(2,3,4-trimethoxyphenyl)cyclopropene-1-thione with oxalyl bromide results in the formation of a species that promotes the glycosylation between 2,6-dideoxy-sugar hemiacetals and glycosyl acceptors in good yield and high α-selectivity. Both reactions are mild and tolerate a number of sensitive functional groups including highly acid-labile 2,3,6-trideoxy-sugar linkages.
Co-reporter:Dr. Jason M. Nogueira;Marissa Bylsma;Danielle K. Bright ; Clay S. Bennett
Angewandte Chemie 2016 Volume 128( Issue 34) pp:10242-10246
Publication Date(Web):
DOI:10.1002/ange.201605091
Abstract
We have found that activating either 2,3-bis(2,3,4-trimethoxyphenyl)cyclopropenone or 2,3-bis(2,3,4-trimethoxyphenyl)cyclopropene-1-thione with oxalyl bromide results in the formation of a species that promotes the glycosylation between 2,6-dideoxy-sugar hemiacetals and glycosyl acceptors in good yield and high α-selectivity. Both reactions are mild and tolerate a number of sensitive functional groups including highly acid-labile 2,3,6-trideoxy-sugar linkages.
Co-reporter:An-Hsiang Adam Chu, Andrei Minciunescu, and Clay S. Bennett
Organic Letters 2015 Volume 17(Issue 24) pp:6262-6265
Publication Date(Web):December 4, 2015
DOI:10.1021/acs.orglett.5b03282
Armed thioglycosides can be activated with aryl(trifluoroethyl)iodonium triflimide in 2:1 CH2Cl2/pivalonitrile or a solvent combination of CH2Cl2, acetonitrile, isobutyronitrile, and pivalonitrile (6:1:1:1) at 0 °C for glycosylation reactions that proceed in good yield and moderate to excellent selectivity (up to 25:1 β/α). Comparison to other common glycosylation promoters reveals that both the mixed solvent and the iodonium salt promoter are required for stereoselectivity.
Co-reporter:John Paul Issa ;Clay S. Bennett
Journal of the American Chemical Society 2014 Volume 136(Issue 15) pp:5740-5744
Publication Date(Web):March 26, 2014
DOI:10.1021/ja500410c
The efficient and stereoselective construction of glycosidic linkages remains one of the most formidable challenges in organic chemistry. This is especially true in cases such as β-linked deoxy-sugars, where the outcome of the reaction cannot be controlled using the stereochemical information intrinsic to the glycosyl donor. Here we show that p-toluenesulfonic anhydride activates 2-deoxy-sugar hemiacetals in situ as electrophilic species, which react stereoselectively with nucleophilic acceptors to produce β-anomers exclusively. NMR studies confirm that, under these conditions, the hemiacetal is quantitatively converted into an α-glycosyl tosylate, which is presumably the reactive species in the reaction. This approach demonstrates that use of promoters that activate hemiacetals as well-defined intermediates can be used to permit stereoselective glycosylation through an SN2-pathway.
Co-reporter:An-Hsiang Adam Chu, Andrei Minciunescu, Vittorio Montanari, Krishna Kumar, and Clay S. Bennett
Organic Letters 2014 Volume 16(Issue 6) pp:1780-1782
Publication Date(Web):March 5, 2014
DOI:10.1021/ol5004059
The air- and water-stable iodonium salt phenyl(trifluoroethyl)iodonium triflimide is shown to activate thioglycosides for glycosylation at room temperature. Both armed and disarmed thioglycosides rapidly undergo glycosylation in 68–97% yield. The reaction conditions are mild and do not require strict exclusion of air and moisture. The operational simplicity of the method should allow experimentalists with a limited synthetic background to construct glycosidic linkages.
Co-reporter:Dina Lloyd and Clay S. Bennett
The Journal of Organic Chemistry 2014 Volume 79(Issue 20) pp:9826-9829
Publication Date(Web):September 11, 2014
DOI:10.1021/jo501472v
A concise gram-scale synthesis of protected colitose thioglycosides for use in bacterial carbohydrate antigen synthesis is described. The synthesis proceeds in six steps and 59–70% overall yield from commercially available l-fucose, making it the most efficient route reported to date. Key steps include regioselective installation of a thiocarbonate using catalytic dioctyltin dichloride (10 mol%) and a tris(trimethylsilyl)silane-mediated radical deoxygenation.
Co-reporter:An-Hsiang Adam Chu, Son Hong Nguyen, Jordan A. Sisel, Andrei Minciunescu, and Clay S. Bennett
Organic Letters 2013 Volume 15(Issue 10) pp:2566-2569
Publication Date(Web):May 6, 2013
DOI:10.1021/ol401095k
A method for the highly selective synthesis of 1,2-cis-α-linked glycosides that does not require the use of the specialized protecting group patterns normally employed to control diastereoselectivity is described. Thioglycoside acceptors can be used, permitting iterative oligosaccharide synthesis. The approach eliminates the need for lengthy syntheses of monosaccharides possessing highly specialized and unconventional protecting group patterns.
Co-reporter:John Paul Issa, Dina Lloyd, Emily Steliotes, and Clay S. Bennett
Organic Letters 2013 Volume 15(Issue 16) pp:4170-4173
Publication Date(Web):August 2, 2013
DOI:10.1021/ol4018547
N-Sulfonyl imidazoles activate 2-deoxy-sugar hemiacetals for glycosylation presumably by converting them into glycosyl sulfonates in situ. By matching the leaving group ability of the sulfonate with the reactivity of the donor, it is possible to obtain β-specific glycosylation reactions. The reaction serves as proof of the principle that, by choosing promoters that can modulate the reactivity of active intermediates, it is possible to place glycosylation reactions entirely under reagent control.
Co-reporter:Son Hong Nguyen, Adam H. Trotta, John Cao, Timothy J. Straub and Clay S. Bennett
Organic & Biomolecular Chemistry 2012 vol. 10(Issue 12) pp:2373-2376
Publication Date(Web):20 Dec 2011
DOI:10.1039/C2OB06883D
The application of the safety-catch linker concept to solid-phase glycoconjugate synthesis is described. The process allows for direct conjugation of resin bound glycans to complex aglycones during cleavage. Large excesses of either coupling partner are not required, and even very hindered alcohols serve as acceptors in the reaction.
Co-reporter:Jason M. Nogueira;John Paul Issa;An-Hsiang Adam Chu;Jordan A. Sisel;Ryan S. Schum ;Clay S. Bennett
European Journal of Organic Chemistry 2012 Volume 2012( Issue 26) pp:4927-4930
Publication Date(Web):
DOI:10.1002/ejoc.201200907
Abstract
A mixture of 3,3-dibromocyclopropene and TBAI promotes highly α-selective glycosylation reactions (up to >20:1) by using deoxy sugar hemiacetal donors. The reaction provides a convenient method for generating highly reactive glycosyl donors in situ from shelf-stable starting materials. Both armed and disarmed sugars undergo the reaction, and selectivity is independent of the configuration of the donor sugar.
Co-reporter:Jason M. Nogueira, Son Hong Nguyen, and Clay S. Bennett
Organic Letters 2011 Volume 13(Issue 11) pp:2814-2817
Publication Date(Web):May 6, 2011
DOI:10.1021/ol200726v
Dehydrative glycosylation reactions using 2-deoxy- and 2,6-dideoxy-sugar donors promoted by a combination of 3,3-dichloro-1,2-diphenylcyclopropene and tetrabutylammonium iodide (TBAI) are described. The reactions are α-selective and proceed under mild conditions at room temperature without the need for special dehydrating agents. The reaction is shown to be effective with a number of glycosyl acceptors, including those possessing acid and base sensitive functionality.
Co-reporter:Son Hong Nguyen, Adam H. Trotta, John Cao, Timothy J. Straub and Clay S. Bennett
Organic & Biomolecular Chemistry 2012 - vol. 10(Issue 12) pp:NaN2376-2376
Publication Date(Web):2011/12/20
DOI:10.1039/C2OB06883D
The application of the safety-catch linker concept to solid-phase glycoconjugate synthesis is described. The process allows for direct conjugation of resin bound glycans to complex aglycones during cleavage. Large excesses of either coupling partner are not required, and even very hindered alcohols serve as acceptors in the reaction.
![Dinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphepin,4-hydroxy-2,6-bis[2,4,6-tris(1-methylethyl)phenyl]-, 4-oxide, (11bS)-](/data/chemimg/103700/874948-63-7.png)
![Dinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphepin,4-hydroxy-2,6-bis[2,4,6-tris(1-methylethyl)phenyl]-, 4-oxide, (11bS)-](/data/chemimg/103700/874948-63-7_b.png)
![Dinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphepin,4-hydroxy-2,6-bis[2,4,6-tris(1-methylethyl)phenyl]-, 4-oxide, (11bR)-](/data/chemimg/115800/791616-63-2.png)
![Dinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphepin,4-hydroxy-2,6-bis[2,4,6-tris(1-methylethyl)phenyl]-, 4-oxide, (11bR)-](/data/chemimg/115800/791616-63-2_b.png)
![α-D-Glucopyranoside, methyl 6-O-[2-deoxy-3,4,6-tris-O-(phenylmethyl)-α-D-arabino-hexopyranosyl]-2,3,4-tris-O-(phenylmethyl)-](/data/chemimg/3761500/117841-70-0.png)
![α-D-Glucopyranoside, methyl 6-O-[2-deoxy-3,4,6-tris-O-(phenylmethyl)-α-D-arabino-hexopyranosyl]-2,3,4-tris-O-(phenylmethyl)-](/data/chemimg/3761500/117841-70-0_b.png)
![α-D-Glucopyranoside, methyl 2,3,4-tris-O-(phenylmethyl)-6-O-[2,3,4,6-tetrakis-O-(phenylmethyl)-β-D-glucopyranosyl]-](/data/chemimg/3739400/56632-57-6.png)
![α-D-Glucopyranoside, methyl 2,3,4-tris-O-(phenylmethyl)-6-O-[2,3,4,6-tetrakis-O-(phenylmethyl)-β-D-glucopyranosyl]-](/data/chemimg/3739400/56632-57-6_b.png)
![α-D-Glucopyranoside, methyl 2,3,4-tris-O-(phenylmethyl)-6-O-[2,3,4,6-tetrakis-O-(phenylmethyl)-α-D-glucopyranosyl]-](/data/chemimg/3739400/55094-26-3.png)
![α-D-Glucopyranoside, methyl 2,3,4-tris-O-(phenylmethyl)-6-O-[2,3,4,6-tetrakis-O-(phenylmethyl)-α-D-glucopyranosyl]-](/data/chemimg/3739400/55094-26-3_b.png)
![α-D-Glucopyranoside, methyl 6-O-[2-deoxy-3,4,6-tris-O-(phenylmethyl)-β-D-arabino-hexopyranosyl]-2,3,4-tris-O-(phenylmethyl)-](/data/chemimg/3761500/117841-71-1.png)
![α-D-Glucopyranoside, methyl 6-O-[2-deoxy-3,4,6-tris-O-(phenylmethyl)-β-D-arabino-hexopyranosyl]-2,3,4-tris-O-(phenylmethyl)-](/data/chemimg/3761500/117841-71-1_b.png)
