Photo-bromination of carbohydrate derivatives. Part 3. C-5 bromination of penta-O-benzoyl-α- and -β-<scp>D</scp>-glucopyranose; a route to<scp>D</scp>-xylo-hexos-5-ulose derivatives and α-<scp>L</scp>-idopyranosides

Ferrier, R. J.; Tyler, Peter C.

doi:10.1039/p19800001528

Cited by 33 publications

(8 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…13 C NMR (125 MHz, CDCl 3 ): δ 66.6 (C‐6), 69.5 (C‐4), 69.9 (C‐2), 71.3 (C‐3), 92.4 (C‐1), 96.6 (C‐5), 128.2, 128.3, 128.4, 128.5(0), 128.5(3), 128.5(8), 129.7, 129.9(6), 129.9(9), 130.1, 130.2, 164.1, 164.5, 165.1(2), 165.1(9), 165.3. The 1 H and 13 C NMR spectra were in accord with the literature [32] . LRMS: m/z 802.6 [M+Na] + .…”

Section: Methodssupporting

confidence: 68%

A Substituent‐Directed Strategy for the Selective Synthesis of L‐Hexoses: An Expeditious Route to L‐Idose

et al. 2021

View full text Add to dashboard Cite

L‐Hexoses are rare but biologically significant components of various important biomolecules. However, most are prohibitively expensive (if commercially available) which limits their study and biotechnological exploitation. New, efficient methods to access L‐hexoses and their derivatives are thus of great interest. In a previous study, we showcased a stereoselective Bu3SnH‐mediated transformation of a 5‐C‐bromo‐D‐glucuronide to an L‐iduronide. We have now drawn inspiration from this result to derive a new methodology – one that can be harnessed to access other L‐hexoses. DFT calculations demonstrate that a combination of a β‐F at the anomeric position and a methoxycarbonyl substituent at C‐6 is key to optimising the selectivity for the L‐hexose product. Our investigations have also culminated in the development of the shortest known synthetic route to a derivative of L‐idose from a commercially available starting material (45 % yield over 3 steps). Collectively, these results address the profound lack of understanding of how to synthesise L‐hexoses in a stereoselective fashion.

show abstract

Section: Methodssupporting

confidence: 68%

A Substituent‐Directed Strategy for the Selective Synthesis of L‐Hexoses: An Expeditious Route to L‐Idose

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Synthesis of the 5-fluoroglycosyl fluorides hinged upon the known radical photobromination reaction at C5 of per-O-acetylated β- and α-glucosyl fluorides. − Fluorination of these 5-bromoglucosyl fluorides and deacetylation afforded products 1 and 2 , which were purified by chromatography and characterized …”

mentioning

confidence: 99%

5-Fluoro Glycosides: A New Class of Mechanism-Based Inhibitors of Both α- and β-Glucosidases

1996

View full text Add to dashboard Cite

Glycosidase inhibitors have proven to be valuable probes of enzymic mechanism 1 and show considerable promise as therapeutic drugs. 2 Design of inhibitors for these enzymes is best based upon a knowledge of their mechanisms. Retaining glycosidases 3 are generally believed 4-6 to follow a doubledisplacement mechanism in which a covalent glycosyl-enzyme intermediate is formed and hydrolyzed Via oxocarbenium ion like transition states, as shown for an R-glucosidase in Scheme 1. A successful strategy for inactivation of retaining -glycosidases involves the use of activated 2-deoxy-2-fluoro glycosides that form a stabilized 2-deoxy-2-fluoroglycosyl-enzyme intermediate that turns over only slowly. Unfortunately, this approach has been notably unimpressive with all R-glycosidases tested. 7,8 Further, the requirement for a fluorine at C2 limits the utility of these inhibitors if the enzyme (e.g., an Nacetylhexosaminidase) is intolerant of substitution at this position. This paper describes a novel approach which obviates both these problems and allows inhibition of both R-and -glycosidases through accumulation of a covalent glycosylenzyme intermediate, without compromising specificity through substitution of any ring hydroxyl. It also provides substantial evidence against an alternative mechanism for retaining glycosidases involving endocyclic ring opening. [9][10][11] 5-Fluoro glycosides with good leaving groups, such as 1 and 2, might be expected to inactivate "retaining" glycosidases by formation of a stabilized 5-fluoroglycosyl-enzyme intermediate through a trapping mechanism analogous to that of the 2-deoxy-2-fluoro glycosides. A sterically conservative fluorine substitution at C5 of a glycosyl oxocarbenium ion exerts electronic effects similar to or greater than those of a C2 fluorine, both atoms being adjacent to centers of developing positive charge. 12 However, crucial transition state binding interactions between the enzyme and the usual C2 substituent [13][14][15] which are disrupted in the case of the 2-deoxy-2-fluoro sugars are still possible for the 5-fluoro glycosides. Synthesis of the 5-fluoroglycosyl fluorides hinged upon the known radical photobromination reaction at C5 of per-Oacetylated -and R-glucosyl fluorides. 16-18 Fluorination of these 5-bromoglucosyl fluorides and deacetylation afforded products 1 and 2, which were purified by chromatography and characterized. 19 Liu, K. K.-C.; Pederson, R. L.; Zhong, Z.; Ichikawa, Y.; Porco, J. A. J.; Wong, C.-H. J. Am. Chem. Soc. 1991, 113, 6187) have indicated that the greatest difference in partial charge between a ground state sugar and the corresponding glycosyl oxocarbenium ion is at O5 rather than C1. Bromination of per-O-acetylated -and R-glucosyl fluorides with N-bromosuccinimide (hν, N-bromosuccinimide, CCl4) yielded the protected 5-bromoglucosyl fluorides. Fluorination (Igarashi, K.; Honma, T.; Irisawa, J. Carbohydr. Res. 1969, 11, 577) of the anomer (AgBF4, toluene) afforded the protected 5-fluoro--D-glucosyl fluoride in low yield. 5-Fluoro-Rgluco...

show abstract

“…4.2.1. 2,3,4,6‐Tetra‐ O ‐acetyl‐α,β‐ D ‐idopyranose (11): 2,3,4,6‐Tetra‐ O ‐acetyl‐α‐ D ‐idopyranosyl bromide ( 10 ) was obtained by a modified literature method 55. To a solution of 1,2,3,4,6‐penta‐ O ‐acetyl‐α‐ D ‐idopyranose33,34 ( 9 ; 11.50 g, 29.5 mmol) in 1,2‐dichloroethane (100 mL), 33 % HBr in acetic acid (30 mL) was added and the mixture was stirred at room temp.…”

Section: Methodsmentioning

confidence: 99%

Synthesis of Lupane‐Type Saponins Containing an Unusual α‐D‐Idopyranoside Fragment as Potent Cytotoxic Agents

et al. 2014

View full text Add to dashboard Cite

A practical method for the preparation of benzoyl protected allyl and benzyl α‐D‐idopyranosides, and D‐idopyranosyl trichloroacetimidate, from 1,2,3,4,6‐penta‐O‐acetyl‐α‐D‐idopyranose, is described. All derivatives can be prepared on a multigram scale and require only simple chromatographic purification. A concise synthesis of lupane triterpenes bearing an unusual D‐idopyranoside fragment is described. All new compounds were evaluated in vitro for their cytotoxic activities. Novel saponins exhibited interesting cytotoxic activity in the micromolar range against human cancer cell lines including T‐lymphoblastic leukemia CEM, breast adenocarcinoma MCF7, and cervical carcinoma HeLa, but also against normal human fibroblasts BJ.

show abstract

Photo-bromination of carbohydrate derivatives. Part 3. C-5 bromination of penta-O-benzoyl-α- and -β-D-glucopyranose; a route toD-xylo-hexos-5-ulose derivatives and α-L-idopyranosides

Cited by 33 publications

References 1 publication

A Substituent‐Directed Strategy for the Selective Synthesis of L‐Hexoses: An Expeditious Route to L‐Idose

A Substituent‐Directed Strategy for the Selective Synthesis of L‐Hexoses: An Expeditious Route to L‐Idose

5-Fluoro Glycosides: A New Class of Mechanism-Based Inhibitors of Both α- and β-Glucosidases

Synthesis of Lupane‐Type Saponins Containing an Unusual α‐D‐Idopyranoside Fragment as Potent Cytotoxic Agents

Contact Info

Product

Resources

About