Mannitol tris , hydrolysis

Less is known concerning the partial, acid hydrolysis of alditol polyacetals derived from ketones, compared to those derived from aldehydes. The acid hydrolysis of 1,2 3,4 5,6-tri-O-isopropylidene-D-mannitol to 3,4-O-isopropylidene-D-mannitol55,56 and of l,2 3,4-di-0-isopropylidene-L-rhamnitol to 3,4-O-isopropylidene-L-rhamnitol57 indicates an order of isopropylidene acetal stability of a-threo > a, and this order is supported by the partial hydrolysis of 2,3 4,5-di-O-isopro-pylidene derivatives of dialkyl dithioacetals of D-arabinose58 and D-xylose59 to 2,3-acetals. 

O-Isopropylidene-D-mannitol [72] is readily prepared by hydrolysis of 1,2 3,4 5,6-tri-O-isopropylidene-D-mannitol and after alkylation gives the 1,2,5,6-tetra-O-alkylmannitol on acidic hydrolysis and this is readily. converted into l,2-di-0-alkyl-L-glycerol (59). The benzyl (59, R = Bn) [73, 74], allyl (59, R = All) [75] and but-2-enyl (59, R = CH2—CH = CH—Me) [75, 76] ethers have been prepared in this way as intermediates for the synthesis of lipids. 

Treatment of the monoethylidene-D-mannitol with lead tetraacetate or periodate resulted in the consumption of two molecular equivalents of oxidant with the concomitant production of one mole of formaldehyde, one mole of formic acid and a monoethylidene-D-erythrose, the latter being identified by its conversion into the known crystalline D-erythrosazone.118 This evidence limited the choice of structure for the mannitol acetal to the 1,3- and 2,3-compound (4,6- and 4,5- are the respective identical structures). Two additional facts eliminated the latter alternative, first, the tetratosyl ester gave only one mole of sodium p-toluenesulfonate when heated with sodium iodide in acetone, and secondly, the same monoethylidene-D-mannitol was obtained from the above 1,3,4,6-diethylidene-D-mannitol by acidic hydrolysis.118 For these reasons Bourne, Bruce and Wiggins118 assigned to the mono-, di- and tri-ethylidene-D-mannitols, respectively, the 1,3-, 1,3 4,6- and 1,3 2,5 4,6- structures. 

The di-(cyclohexylidene)-D-mannitol contained a terminal a-glycol group because (a) oxidative scission with lead tetraacetate consumed one mole of the oxidant and gave one mole of formaldehyde, together with an acid-labile derivative of D-arabinose, and (b) its dimethyl ether yielded the known crystalline 5,6-dimethyl-D-mannitol (1,2- is identical) when heated with aqueous acid.1 0 Since graded acidic hydrolysis of the diketal furnished 3,4-cyclohexylidene-D-mannitol,3 it must have possessed the 1,2 3,4-structure and the parent triketal must have been 1,2 3,4 5,6-tri-(cyclohexylidene)-D-mannitol. 

Alternatively, the synthesis of 23 from D-mannitol has been started by acetalation with benzaldehyde to give l,3 4,6-di-C -benzylidene-D-mannitol (74) (58%), which was tri-flated to form the ditriflate 75 (95%) (Scheme 13). Nucleophilic substitution of the ditriflate groups in 75 with anhydrous hydrazine afforded compound 77, which was hydrogenated over Raney nickel to give the protected pyrrolidine 78 (1(X)%), which upon acid hydrolysis gave 23. 

Stepwise hydrolysis of tri- 0-isopropylidene-D-mannitol was carried out by Irvine and Patterson as follows 84... 

As starting materials for the synthesis of the enantiomers of glyceraldehyde, D-mannitol and L-ascorbic acid have already been mentioned which are inexpensive commercial products. From D-mannitol, not only the l,2 5,6-diprotected d-2, but also the tri-0-isopiopylidene derivative can be obtained2,23 partial hydrolysis leads to 3,4-0-isopropylidene-D-mannitol23. By careful control of the reaction conditions, 1,2-0-isopropylidene-D-mannitol is formed from D-mannitol and the methyl enol ether of acetone24. 

A short synthesis of 3,4,6-tri-0-benzyl-l,5-dideoxy-l,5-imino-D-mannitol has been achieved by acid-catalysed hydrolysis, followed by controlled reductive amination of a per-benzylated l,6 -diazido-l,6 -dideoxy-sucrose derivative. Further transformation by way of an azide displacement of a 2-0-triflyl derivative afforded ultimately 2-acetamido-l,2,5-trideoxy-l,5-imino-D-glucitol (2-acet-amido-1,2-dideoxynojirimycin). ... 

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