Periodate oxidation/borohydride

L-Arabinose was formed on periodate oxidation, borohydride reduction, and mild, acid hydrolysis of the pentasaccharide, demonstrating that it contains a D-galactofuranosyl residue. The amino sugar residue was resistant to periodate oxidation but was oxidized after N-deacetylation, showing that this residue is substituted at 0-4, not at 0-3. The structure of the pentasaccharide 21 was thereby established. It showed [a]D —36°, indicating that all sugar residues are /3-D-linked. 

It is possible to degrade 2-amino-2-deoxyhexoses to 2-amino-2-deoxy-pentoses by means of chain-shortening reactions from the nonreducing end of the molecule. Thus, Wolfrom and Anno38 converted ethyl 2-acetamido-2-deoxy-1 -thio-a-d-glucofuranoside (XV) into 2-amino-2-deoxy-a-D-xylose hydrochloride (XVI) by sequential application of periodate oxidation, borohydride reduction, and hydrolysis, as in the following reaction scheme. 

Convenient and high-yielding procedures have been described for the periodate oxidation-borohydride reduction of N-acyl-5 -0-monoethoxy-trityl ribonucleosides. 

The periodate oxidation/reduction approach has also been used to differentiate between the methyl a- and p-glycosides of N-acetylneuraminic acid. Only the C7-analogue of the p-anomer could be lactonized (Yu and Ledeen 1969). The preparation of the C7-analogue of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid using periodate oxidation/borohydride reduction was reported by Meindl and Tuppy (1970). 

Deoxy-l-fluoro-L-glycerol (18) has been prepared by, among other methods, the treatment of 3,4-0-benzylidene-2,5-0-methylene-l,6-di-O-p-tolylsulfonyl-D-mannitol107 (17) with tetrabutylammonium fluoride in acetonitrile, followed by removal of the benzylidene group, periodate oxidation, reduction with borohydride, and hydrolysis. 1,6-Dideoxy-l,6-difluorogalactitol108 was obtained by treatment of 2,3 4,5-di-0-isopropylidene-l,6-di-0-(methylsulfonyl)galactitol with tetra-... 

Finally, Droge and coworkers26 showed that the 2-aminoethyl phosphate-substituted KDO group is the lateral KDO unit of the branched trisaccharide (see Fig. 7), as follows. LPS from Salmonella minnesota mR3 was subjected to periodate oxidation. This sample, together with a control that had not been oxidized, was then mildly hydrolyzed with acid (pH = 3.4) during 1 h at 100°. Following removal of lipid A, both samples were analyzed by gel-filtration on Sephadex G-10, and paper electrophoresis. As expected, the ninhydrin-positive material obtained from the control sample was identical with KDO 7-(2-aminoethyl phosphate) (17) as previously identified. This spot was absent from the periodate-treated sample. Instead, an almost neutral, ninhydrin-positive spot was observed. This material (compound 26) was eluted, subjected to reduction with sodium [3H]borohydride, and hydrolyzed under strongly acidic conditions (see Scheme 11). Fol-... 

Lemer (29) reported a simple synthesis of L-erythrose that involves 2,3-di-O-isopropylidene-D-gulono-1,4-lactone (7b) as a key intermediate. Reduction of the lactone group of 7b with sodium borohydride, followed by periodate oxidation of the L-glucitol derivative, afforded 2,3-O-isopropy-lidene-L-erythrose. The free sugar may be readily obtained by acidic hydrolysis of the latter. 

Periodic acid oxidation has proved to be a very useful tool in enzymology since a wide variety of biochemicals contain hydroxyl groups on adjacent carbon atoms. For example, periodate-oxidized ATP (also called adenosine 5 -triphosphate 2, 3 -dialdehyde) has often been used as an alternative substrate or an irreversible inhibitor for a wide variety of ATP-utilizing enzymes. This compound, and many others, are now commercially available, even though they are readily synthesized e.g., periodic acid oxidized ADP, AMP, adenosine, P, P -di(adenosine-5 )pentaphosphate, P, P -di(adenosine-5 )tetraphos-phate, GTP, GDP, GMP, guanosine, CTP, CDP, CMP, etc. In the case of the nucleosides, commercial sources also can supply the dialcohol form of the nucleoside i.e., the nucleoside has first been oxidized with periodic acid and then reduced to the dialcohol with borohydride. 

Reduction of the furan (152) with sodium borohydride gave diol 154 and its cyclization (P2SJ/CS2) formed 19% of sulfide (155). Periodate oxidation of 155 gave (92%) the corresponding sulfoxide (156). The latter reacted with dimethyl acetylenedicarboxylate forming the adduct 157 (70%) the formation of 157 is evidence of the presence of the thieno[3,4-c]furan system (158) as an intermediate. Cyclization of diketone 153 in the presence of phosphorus pentasulfide proceeds M. P. Cava and M. A. Sprecker, J. Amer. Chem. Soc. 94, 6214 (1972). 

L-Mannitol does not occur naturally but is obtained by the reduction of L-mannose or L-mannonic acid lactone (80). It can be synthesized from the relatively abundant L-arabinose through the L-mannose and L-glucose cyanohydrins, conversion to the phenylhydrazines which are separated, liberation of L-mannose, and reduction with sodium borohydride (81). Another synthesis is from L-inositol (obtained from its monomethyl ether, quebrachitol) through the diacetonate, periodate oxidation to the blocked dialdehyde, reduction, and removal of the acetone blocking groups (82). 

Deamination studies have aided attempts to locate the positions of the O-sulfate groups in heparin. From the results of deamination and periodate-oxidation studies, it was concluded239 that half of the uronic acid residues are sulfated at C-2, and sequential periodate oxidation, reduction with sodium borohydride, acid treatment, and deamination gave 2,5-anhydro-D-mannose 6-sulfate.240,241 Sulfated O-(hexosyluronic acid)-2,5-anhydro-D-mannose and sulfated uronic acids were subsequently isolated, and the isolation (in 65% yield) of the disulfated 0-(idosyluronic acid)-2,5-anhydro-D-mannose (137) from heparin, together with the 13C n.m.r. spectra of 137 and heparin, suggested243 that at least two thirds of the heparin structure consists of the repeating unit 138. 

The Smith degradation4 involves reduction of the periodate-oxidized polysaccharide with borohydride, followed by mild hydrolysis with acid. (The periodate oxidation has already been treated in Section 111,1, p. 200.) The modified sugar residues contain acyclic acetal groupings, which are hydrolyzed much faster than the glyco-sidic linkages. The product therefore contains small fragments (such... 

Whereas ethyl l-thio-d-D-arabinofuranoside cannot be prepared directly, the 5-O-benzoyl diethyl dithioacetal gave 38% of ethyl 5-O-benzoyl-l-thio-0-D-arabinofuranoside, which was debenzoylated to the desired product. The 5-benzoate of ethyl 1-thio-a-D-ribofuranoside was similarly prepared.88 Two other compounds, ethyl 2-acetamido-2-deoxy-l-thio-/3-L-arabino-furanoside72 and ethyl 2-acetamido-2-deoxy-l-thio-a-D-xylofuranoside,73 were prepared from the corresponding d-galacto and d-gluco analogs by periodate oxidation, and subsequent borohydride reduction of the product. 

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