Helferich conditions

By glycosylation of 19 with the halide 20 following Helferich conditions (HgBr2, HgO), a typical but acceptable amount of the desired a-glycoside 21 (40%) of a 2,6-dideoxy sugar in the L-series was obtained which represents the A-B disaccharide unit of aclacinomycin A [8],... 

Alternatively, 4,6-di-O-benzylidene protection can be introduced in 10 under controlled acid-catalysis not affecting the fe/t-butyl ester. The obtained monofunctional compound 12 reacts with protected galactosyl bromides 14 under Helferich conditions to give T-antigen threonine building blocks 15. ... 

Linear Homotetrasaccharides.- Cyclo-oligomerisation of the isomeric (8) and (9) under Helferich conditions gave the unbranched tetramers (lO) and (11), respectively, as well as the dimer and trimer from the latter trityl ether. 

Perhaps the earliest report of the replacement of a sulfonate ester attached to a secondary carbon atom in a sugar derivative was that of Helferich (53). Under quite drastic conditions (sodium iodide in acetone, 105°C., 72 hours, sealed system) the 4-mesylate derivative 9 was converted into a crystalline 4-deoxy-4-iodo sugar derivative 10 in 46% yield. Although the position of the iodine atom was established, the configuration at C-4 was not known. 

The disaccharide derivative 0-(2,3,4,6-tetra-0-acetyl-/ -D-galactopy-ranosyl)-(l— 3)-0-(2-acetamido-6-0-benzoyl-2-deoxy-/ -D-glucopyran-osyl)-(l— 3)-N-(benzyloxycarbonyl)-L-serine methylamide (192) was prepared by condensation of 3-0-(2-acetamido-2-deoxy-6-0-benzoyl-/ -D-glucopyranosyl)-N-(benzyloxycarbonyl)-L-serine methylamide (191) with tetra-O-acetyl-a-D-galactopyranosyl bromide147 (110) under the conditions of the Helferich-Wedemeyer procedure. Treatment of 192 with methylamine in methanol at 0° gave89 193. 

In cm empirical approach (Helferich modification) it has been demonstrated on many occasions that mercuric salts (cyanide or bromide usually) in polar solvents such as nitromethane or acetonitrile favour the formation of a-glucosides, conceivably because under these conditions the mechanism of the halide displacement is rmimolecular and the carbonium ion can be approached from either side o). 

Starting with /jemi-acetal 12 the anomeric center has to be protected. Under acidic conditions in methanol the C-l methyl ether is obtained as a mixture of anomers. Therefore the a-anomer is favored because of the anomeric effect (see p. 251). Separation of the two anomers by crystallization is possible. This reaction is connected to the research of E. Fischer (Fischer-Helferich method).13... 

According to Klingensmith and Evans,either of the enantio-morphous acetylribosyl bromides reacts with dihydroxyacetone monoacetate, AcOCHj.CO.CH2OH, in benzene solution, under conditions established by Reynolds and Evans, using iodine as a catalyst after the manner of Helferich, Bohm and Winkler. The reaction gave rise to needle-like clusters of 3,4-diacetyl-D-ribose 3 -acetoxyacetonyl 1,2-orthoacetate (VIb), with in. p. 97-98° (corr.) and [a]o —11.6°, or the corresponding L-compound with the same m. p. and [q ]d -j-11.8°. 

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