Vilsmeier-haack reactoin of glycals-a short route to C-2-formyl glycals☆

Synthesis and reactions of unsaturated sugars.

Abstract: Publisher Summary This chapter discusses the synthesis and reactions of unsaturated sugars. Sugar derivatives that contain double bonds have been developed and used so extensively that they almost certainly constitute the most versatile category of carbohydrate compounds available for use in synthesis of unsaturated sugars. They may be applied both in the synthesis of complex members of the family and of a myriad enantiomerically pure noncarbohydrate compounds—notably, many of interest in medicinal chemistry. In addition, some unsaturated sugar derivatives have themselves been found to possess important therapeutic properties. The unnatural L-nucleoside inhibits reverse transcriptase and shows potent and selective anti-AIDS activity. This chapter surveys the chemistry of most of the important types of monosaccharide derivatives that contain single alkene groups—notably, the glycols that are extremely valuable starting materials for a vast range of synthetic transformations. It also discusses the preparation of the reactions of glycols, elaborates the synthesis of pyranoid and furanoid 2- and 3-Enes, and explains the chemistry of endo-Enes and exo-Enes.

Synthesis and evaluation of pyrazolo[3,4-b]pyridines and its structural analogues as TNF-α and IL-6 inhibitors

Abstract: In the present article, we have synthesized three different series of pyrazolo[3,4-b]pyridines and their structural analogues using novel synthetic strategy involving one-pot condensation of 5,6-dihydro-4H-pyran-3-carbaldehyde/2-formyl-3,4,6-tri-O-methyl- d -glucal/chromone-3-carbaldehyde with heteroaromatic amines. All synthesized compounds were evaluated for their anti-inflammatory activity against TNF-α and IL-6. Out of 28 compounds screened, 40, 51, 52 and 56 exhibited promising activity against IL-6 with 60–65% inhibition at 10 μM concentration. Amongst these, 51, 52 and 56 showed potent IL-6 inhibitory activity with IC50’s of 0.2, 0.3 and 0.16 μM, respectively. Compound 56 was not cytotoxic in CCK-8 cells up to the concentration of >100 μM.

2‐C‐Formyl Glycals: Emerging Chiral Synthons in Organic Synthesis

Abstract: Naturally occurring carbohydrates and their derivatives have been useful during the last few decades as “chiral pool” constituents in the enantioselective synthesis of biologically active natural and non-natural products. The ready availability of a wide range of carbohydrates in nature and their multichiral architecture, coupled with their well defined stereochemistry, make them attractive starting materials in organic synthesis. The synthesis of key intermediates by incorporation of suitable functional groups onto carbohydrates, which can then be further exploited, has always been a challenging task. In this context, 2-C-formyl glycals, a new class of carbohydrates incorporating an α,β-unsaturated carbonyl system, have recently emerged as potential synthons for numerous organic transformations. Four different syntheses of 2-C-formyl glycals have been reported so far. However, the importance of 2-C-formyl glycals has become well established after our development of a more general, one-step synthesis, employing the well known Vilsmeier−Haack reaction. Synthetic transformations of these 2-C-formyl glycals have resulted in a variety of new compounds of significant synthetic and biological interest. 2-C-Formyl glycals have been shown to be ideal substrates for chemo-, regio- and stereoselective glycosidation, nucleophilic addition/substitution and cycloaddition reactions. The reported syntheses and applications of these important “chiral intermediates” are presented. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

The particular sensitivity of silyl ethers of D-glucal toward two Vilsmeier-Haack reagents POCl3.DMF and (CF3SO2)2O.DMF. Their unique and selective conversion to the corresponding C(6)-O-formates.

Abstract: The two electrophilic Vilsmeier−Haack reagents POCl3·DMF 2 or (CF3SO2)2Ο·DMF 3 mediate the one-step and selective conversion of O-triethylsilyl (O-TES), O-tert-butyldimethylsilyl (O-TBDMS), O-tert-butyldiphenylsilyl (O-TBDPS), and O-triisopropylsilyl (O-TIPS) ethers of d-glucal to the corresponding C(6)-O-formates.

Facile Aza‐Claisen Rearrangement of Glycals: Application in the Synthesis of 1‐Deoxy‐L‐iminosugars

Abstract: 2-C-Methylene-N-glycosyl amides have been obtained from 2-(hydroxymethyl)glycals through a facile aza-Claisen rearrangement. This rearrangement has also been utilized in the synthesis of L-allo-deoxynojirimycin, a moderate inhibitor of human lysosomal α-mannosidase (IC50 = 64 μM), and two new C-5-(hydroxymethyl) analogues of L-altro-deoxynojirimycin and L-ido-deoxynojirimycin.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Die Konstitution der Lycotetraose

Abstract: Das Tetrasaccharid Lycotetraose, das im Tomatin mit Tomatidin verknupft ist, lies sich strukturell aufklaren, indem 1. Tomatin, 2. das daraus durch Abspaltung von D-Xylose gewonnene Glykosid (β1-Tomatin) und 3. das xylosefreie Trisaccharid (Lycotriose), letzteres nach katalytischer Hydrierung zum Lycotriit, mit Methyljodid und Silberoxyd in Dimethylformamid permethyliert wurden. Aus den Spaltstucken der permethylierten Verbindungen, die kristallisiert erhalten wurden, ergibt sich fur die Lycotetraose die verzweigte Konstitution einer β-D-Glucopyranosyl(1 2Glucose)-β-D-xylopyranosyl(1 3Glucose)-β-D-glucopyranosyl(1 4Galaktose)-α-D-galaktopyranose und damit fur das Tomatin die Formel I. Auch aus Demissin last sich, unter Abspaltung von D-Xylose und des Aglykons, kristallisierte Lycotriose gewinnen.

Studies on unsaturated sugars with particular reference to the synthesis of 6-Deoxy-6-fluoro derivatives

Abstract: Three fluoro-substituted unsaturated sugars have been synthesized by transformations within the D-glucal and ethyl 2,3-dideoxy-α-D-erythro-hex-2-enopyranoside series. A number of the intermediate unsaturated sugars not previously described have been characterized. The advantages of the t-butyldimethylsilyl blocking group in such syntheses are described.

The preparation of C-arylglycals. The palladium-catalyzed coupling of 3,4,6-tri-O-(tert-butyldimethylsilyl)-1-(tributylstannyl)-D-glucal and aryl bromides

Abstract: The palladium-catalyzed couplings of the protected 1-(tributylstannyl)-D-glucal 1 and substituted aryl bromides provide the corresponding C-arylglucals and a dimer

A Rapid Route to Hex-1-enopyran-3-uloses

Abstract: Whereas the pseudo-axial 3-hydroxyl group of allal derivatives is known to be inert to manganese dioxide oxidation, the equatorial counterpart in glucal derivatives is shown to be readily oxidized. Thus glucal is converted to the 6-O-triphenylmethyl ether or 6-O-benzoyl ester to promote solubility in chloroform, and the derivatives are oxidized in that solvent in 12 h or less.Acetonation of glucal is readily accomplished in 45 min using 2,2-dimethoxypropane and p-toluenesulfonic acid in dimethylformamide; the product may be oxidized directly either with manganese dioxide or dipyridine chromium oxide. Thus it is possible to obtain 1–3-g quantities of the crystalline acetonated enone from triacetyl glucal (via deacetylation, acetonation, and oxidation) in 3–4 h.If the acetonation medium stands for 2 h methyl 2,3-dideoxy-4,6-O-isopropylidene-α-D-erythro-hex-2-enopyranoside is obtained. The mechanism of its formation in the reaction medium is discussed.