Glucal, preparation

A further example has been given of the synthesis of a 2-deoxy-aldose by the addition of water to a glycal, but, as this reaction is known to be accompanied by competing eliminations,1 it is being replaced in synthetic work by more-specific addition procedures, for example, methoxymercuration (see p. 210). From the 4-deoxy derivative of D-glucal, prepared by standard procedures from 2,3,6-tri-O-acetyl-4-deoxy-D-xy/o-hexopyranosyl bromide, 2,4-dideoxy-D-threo-hexose was obtained.35... 

In similar manner 3,6-dideoxyhexoses have been prepared from esteri-fied 6-deoxy-2-hydroxyglycals. 2,3,4-Tri-0-acetyl-6-deoxy-2-hydroxy-D-glucal was converted into the a and / forms of l,2,4-tri-0-acetyl-2,3-didehydro-3,6-dideoxy-D-en/t/iro-hexose. The a anomer was the main product (77%, 55% isolated crystalline) and, in addition to the ft anomer (19%), a small amount (4%) of saturated products was obtained. On hydrogenation, the major product also suffered some hydrogenolysis but afforded two tri-0-acetyl-3,6-dideoxyhexoses which were shown by NMR spectroscopy to be present in the ratio 12 13 and to have the a configuration. Deacetylation of the reduction products gave... 

All derivatives used were prepared by essentially standard literature procedures and had physical constants in accord with previously reported values. Furthermore, the P.M.R. spectra were in each case consistent with the assigned structures. All solutions were concentrated under reduced pressure and m.p. s are uncorrected. (I) 2-Deoxy-D-arafczno-hexopyranose was a commercial sample from Pfanstiehl Lab. Inc., Waukegan, Illinois and was used without further purification. (II) 3, 4, 6-Tri-O-acetyl-D-glucal (1) was a commercial sample from Aldrich Chem. Co., Milwaukee, Wisconsin and was purified by distillation and recrystallized three times from aqueous ethanol. (Ill) 1, 3, 4, 6-tetra-0-acetyl-2-deoxy-a-D-arahino-hexopyranose (4) was prepared by the method of Bonner (11) while the corresponding / -anomer (5) was synthesized following the procedure of Overend, Stacey, and Stanek (47). (IV) 5, 6-Dideoxy-1, 2-0-isopropylidene-a-D-xj/io-hex-5-enofuranose (20) was provided by A. Rosenthal and G. Khan of this Department. 

Xenon [ F]difluoride was synthesized by isotopic exchange between XeF2 and H F, Si F4, or As F, and F-2DFG was prepared - by the action of this reagent on tri-O-acetyl-D-glucal (61). In this reaction, the combination of ethyl ether (as the solvent) and BFj (as the Lewis acid catalyst) was found to give the best result. ... 

Preparation of F-2DFG through the reaction of tri-C>-acetyl-D-glucal (61) and Xe F2 has been reported - (see Section 11,5). In 1985, a question was raised concerning the purity of the synthetic F-2DFG thus far reported. Thus, van Rijn and coworkers " clarified, by t.l.c. (NaH2P04-impregnated silica plates) and h.p.l.c. analysis, that the addition reactions of AcOF to... 

Simple analogs of an aminoglycoside antibiotic, 2,6-dideoxy-4-0- (671) and -5-0-(2,3-dideoxy-2-fluoro-o -D-r/Z>o-hexopyranosyl)streptamine (672) were prepared by coupling of tri-O-acetyl-2-fluoro-D-glucal (666) with cyclitol derivatives 668 or 667 (through 669 and 670) as shown. 

Glycals are also available from 2-deoxy sugars by acid- or base-induced eliminations ofanomeric substituents. These methods are limited by the availability ofthe 2-deoxy sugars, for which the glycals themselves are the most obvious synthetic precursors. However, examples of these methods (Scheme 5.43) are in the direct preparation oftri-O-benzyl-D-glucal (14) from 2-deoxy-tri-O-benzyl-D-glucopyranose (13) via its 1-O-mesylate [117], and di-O-benzyl-D-ribal (16) from the phenylselenide 15 via oxidation to the selenoxide followed by elimination [118]. 

Unusually-substituted deoxy sugars are found in a number of biologically important natural products, and an application of iodoglycosylation for the preparation of these compounds is shown in Scheme 5.51 [142]. Protected glucals 1 or 14 were selectively converted into 2-deoxy-2-iodo-a-mannopyranosyl glycosides 56 or 57. The... 

Zervas48 through the catalytic reduction of 2,3,4,6-tetraacetyl-2-hydroxy-D-glucal, has recently been prepared by the reductive desulfurization of ethyl tetraacetyl-l-thio-/ -D-mannopyranoside (XL),47 a substance which has been obtained through the mercaptolysis of mannosidostreptomycin48 and may be prepared through the prolonged action of ethyl mercaptan and hydrochloric acid on D-mannose. 

Unsaturated branched-chain sugars were synthetized with 72-84 % yield from both protected and unprotected 2-bromo-D-glucal with methyl acrylate in CH3CN/H2O 5/1 or in DMF/H2O 5/1 with a catalyst prepared from [Pd(DBA)2] and P(o-tolyl)3. Et3N or K2CO3 + /1-BU4NHSO4 could be used as base with similar results. 

Glycals, for example D-glucal (23), being vinyl ethers are susceptible to acid catalysed additions of alcohols which result in the formation of 2-deoxyglycosides, but elimination reactions accompany additions of this type 86) go such products are better prepared by way of halogen adducts or by the alkoxymercuration reaction (see below). On the other hand, the addition procedure can be more suitable than the alcoholysis... 

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