Glycals hydration

Clearly compound 26 (R = Ac) had undergone a reaction analogous to the glycal rearrangement. It has been demonstrated that the rearrangement of this compound also occurs at room temperature in acetic anyhydride in the presence of zinc chloride (34). Under these conditions, however, a further slower isomerization takes place and a third product, assigned the acetylated enone-hydrate structure 29, was isolated. As noted later this structure has been shown to be incorrect. 

Studies with other glycosidases " " showed, however, that effective inhibition by glycals is not a general phenomenon, and that inhibition does not correlate well with hydration to 2-deoxy-o-hexoses. Based on kinetic considerations, the interaction of glycosidases with D-glycals (A) can be described by the following scheme ... 

Hydration or elimination of glycals. Glycals can undergo hydration or elimination when treated with HgS04 in dilute sulfuric acid or aqueous acetic acid.1 However, D-glucal 1 is converted only into the (l,2-dihydroxyethyl)furan (2).2 This product has been used for a short synthesis of L-hexoses. Thus 2 can be converted to the monobenzoate 3 with inversion (Mitsunobu). This product is converted into... 

The classical method of preparing 2-deoxy sugars by hydration of glycals has been adapted51 for the synthesis of 2-deoxy-D-arabino-hexos e-2-t. 

The most common method for the preparation of pyrazoles from other heterocycles is from pyranone-type compounds. Condensation of 2,3-dihydro /7-pyran -ones 787 with various aryl hydrazines in the presence of montmorillonite KSF clay under mild conditions proceeded rapidly to afford enantiomerically pure 5-substituted pyrazoles 788 (Equation 172) <2004TL6033>. Comparable results were obtained when arylhydrazines were reacted with 2-formyl glycals under microwave irradiation <2004TL8587>. Phenylhydrazine and hydrazine were reacted with 3-acetyl-4-hydroxy-6-methyl-2/7-pyran-2-one to afford 4-acetoacetyl-3-methylpyrazolin-5-ones, which were employed in the synthesis of bipyrazoles and pyrazoloisoxazoles <1999JHC1291>. Reaction of 3,3-dialkyl-6-(trifluoromethyl)-2,3-dihy-dro -pyrones with hydrazine hydrate afforded 3-(trifluoromethyl)-5-substituted-pyrazoles <1998RCB1365>. 

The 2-phenylsulfinyl glucal 111 is available from glucal 110 by addition of phenylsulfenyl chloride, DBU elimination and oxidation. The Cl-substituted glycal 113, obtained by addition of the lithium reagent 112 to aldehydes, is transformed to a 8-D-C-glucosyl derivative 114 by reductive removal of the phenylsulfinyl group with Raney nickel and stereoselective hydration of the C/C double bond by hydroboration-oxidation. 

As might be expected, in the absence of acceptors the 2 -deoxyribosyl-enzyme slowly hydrolyses intriguingly, however, the hydrolysis is associated with the production of substantial quantities of ribal, which is then slowly hydrolysed. Formation of ribal is clearly the near microscopic reverse of the first step in the hydration of glycals by retaining glycosidases (Figure 5.21), for some reason favoured with a 2-deoxy substrate. 

Glycals have been successfully used to tag active site amino acids. Denatur-ation of Aspergillus wentii )3-glucosidase Aj in the presence of D-glucal traps the hydrated product bound as an aspartate ester (62). The residue is apparently the same /8-glucosidase aspartic acid labeled with the site-directed irreversible inhibitor conduritol B epoxide (63, 64). 

As in the hydration of glycals, competing elimination reactions interfere. 5-Methoxylevulaldehyde dimethyl acetal (13) and 2-(hydroxymethyl)-5-(methoxymethyl)furan (14), respectively, have been reported as having been found amongst the products of reaction of methanolic hydrogen chloride with n-xylal and n-glucal, respectively, and evidence for the production of 4,5-dihydro-4-hydroxy-2,5-bis(methoxymethyl)furan (15) in the latter reaction has been obtained. The mechanism of formation of these substances has not yet been discussed. 

They observed mainly a-glycoside products in their examples using glycals with all equatorial substituents. Danishefsky [84] has obtained, in allal series, a P-glycoside with the BMLF protocol. Earlier physical organical studies had shown that the hydration of enol ethers occurs via an AdE2 (addition-electrophilic-bimo-lecular) mechanism, i.e., a first step of protonation to form an oxocarbenium ion followed by a second step of nucleophilic addition [85, 86] (Fig. 5.45). 

Regioselective deprotection of per(monochloroacetyl)glycals by hydrazine hydrate occurs at 0-4. In this way 4-0-unprotected esters were made from D-galactal, D-glucal and L-rhamnal, and 4-acetates were then derived by acetylation followed by dechloroacetylation by use of thiourea. ... 

---