Hexofuranoses

The mass spectra of methyl 3-deoxy-p-v-tkreo-pentopyrano-side, methyl 4-deoxy-j3-T>-thieo-pentopyranoside, and 5-deoxy-fi-D-xylo-furanoside are discussed and compared fragmentation paths are sufficiently different to allow identification on the basis of their mass spectra. On the other hand, the mass spectra of methyl 2- and 3-deoxy-5-O-methyl-f3-i>-erythro-pentofuranosides do not exhibit fragmentation differences. The mass spectra of 3-deoxy-l,2 5,6-di-O-isopropylidene -d-xylo - hexofuranose, 5- deoxy -1,2-0-isopropylidene-D-xy o-hexofuranose, and 6-deoxy-l,2-0-iso-propylidene-D-glucofuranose show prominent differences, even between the 5- and 6-deoxy isomers. The interpretation of the spectra was aided by metastable-ion peaks, mass spectra of DzO-exchanged analogs, and the mass spectrum of an O-isopropylidene derivative prepared with acetone-d6. 

The remaining derivatives, 3-deoxy-l,2 5,6-di-0-isopropylidene-D-xt/Zo-hexofuranose (34,39) (9) and 5-deoxy-l,2-0-isopropylidene-D-xt/Zo-hexofur-anose (23, 41) (11), together with the previously mentioned 10 comprise... 

Figure 8. Mass spectrum of 5-deoxy-l,2-0-isopropylidene-T>-xy o-hexofuranose...

In the mass spectrum (Figure 6) of 3-deoxy-l,2 5,6-di-0-isopropyli-dene-D-xt/Zo-hexofuranose (9) the fragmentations described above are found at m/e 229, 171, 143, 111, and 101. The fragments at m/e 143 and 101 arise by cleavage of C-4-C-5 with charge retention on C-4 and C-5, respectively (see Equations 17 and 18). Scheme 2 summarizes the losses of a methyl group, acetone from the second cyclic ketal function, and... 

In the mass spectrum (Figure 8) of the corresponding ketal of 5-deoxy-D-xt/Zo-hexose, 5-deoxy-l,2-0-isopropylidene-D- rt/Zo-hexofuranose (11), the peak from C-4-C-5 cleavage, m/e 159, is of minor relative intensity. Since the ions at m/e 159 are the same from both isomers, 10 and 11, the intensity difference must be attributable to the lower stability of the primary radical formed from C-5 of 11 compared with the secondary radical from 10 ... 

Acetyl-5-deoxy-a-D-xy/o-hex-5-ynofuranose or 6-0-acetyl-5,5,6,6-tetradehydro-5-deoxy-a-D-xy/o-hexofuranose... 

Ci7H26N207 3-(S)-Acetamido-spiro-3,4 -(R)-(3-deoxy-l,2 5,6-di-0-isopro- pylidene-a-D-rifoo-hexofuranose-3-yl)-2-pyrrolidinone SHFSAP 38 469... 

The potentialities of this method are such that, with the proper choice of hexofuranose derivative, access can be gained to 2,5-anhydroaldoses in which the side chains have the cis orientation, as would be required for further elaboration into C-nucleosides. Matsui and coworkers62 reported the synthesis of modified C-nucleosides by acidic treatment of 3-0-benzyl-l,2-0-isopropylidene-5,6-di-0-(methylsulfonyl)-/3-L-talofuranose (60), to give 2,5-anhydro-3-0-benzyl-6-0-(methylsulfonyl)-aidehydo-D-allose dimethyl acetal (61). 

For the depiction of structural formulas of hexofuranoses, a combination of a three-dimensional, Haworth-perspective tetrahydrofuran ring with a Fischer projection of the C-5-C-6 side-chain is commonly used, as exemplified by formulas 3 and 6. With the formal closure of the second ring and formation of a 2,6-dioxabicyclo[3.3.0]octane system, however, the depiction of the C-6-C-3 ring, as in formula 7, also assumes three-dimensional geometry, and this does not correspond to the Fischer projection rule.11 Consequently, structural representations of such bicyclic molecules should be as close as possible to the actual steric situation, as shown by structures 4 and 8. 

Di-0-isopropylidene-a-D-rtbo-hexofuranos-3-ulose (100) was treated with (chlorofluoromethylene)triphenylphosphorane (prepared by reaction of triphenylphosphine on difluorocarbene generated in situ by reaction of potassium ferf-butoxide with dichloro-fluoromethane), to give cis- and rans-3-C-(chlorofluoromethylene)-3-deoxy-l,2 5,6-di-0-isopropylidene-a-D-ribo- (101 and 103) and -xyfo-hexofuranoses (105 and 107), which, on treatment with lithium aluminum hydride, gave cis- and frans-3-deoxy-3-C-(fluoromethyl)-1,2 5,6-di-O-isopropylidene-a-D-rtbo- (102 and 104) and -xyZo-hexofura-... 

Several observations regarding this aspect have been published, and are briefly mentioned here. 5,6-Dideoxy-6-C-phosphono-D-arabino-hexofuranose (135), an isosteric phosphonate analog of D-arabinose 5-phosphate, is apparently converted, in the presence of enolpyruvate phosphate, into 3,8,9-trideoxy-9-C-phosphono-D-mcmno-2-nonulosonic acid (136) under catalysis by KDO 8-phosphate synthetase from Escherichia coli K 235. Compound 136, an isosteric phosphonate analog of KDO 8-phosphate, is a product inhibitor of the synthetase, and, by the nature of the phosphonate group, is not subject to dephosphorylation as catalyzed by KDO 8-phosphate phosphatase156 (see Scheme 40). Compound 119 (see Scheme 33) is a weak inhibitor of KDO 8-phosphate synthetase.81 KDO inhibits KDO 8-phosphate phosphatase,139 and D-ribose 5-phosphate has an inhibitory... 

Trideoxy sugars have also been prepared from aldono- 1,4-lactones. Thus, 2-0-benzoyl-3,5,6-trideoxy-a-D,L-t/ira>hexofuranose was obtained (202) from L-rhamnono- 1,4-lactone via the furanone 155. L-Rhamnono-1,5-lac-... 

More recently, another methodology for sugar-fused butyrolactones employing glycal-derived cyclopropane precursors has been described by Chandrasekaran and co-workers (Scheme 44) [215]. In this case, hexofuranose- or hexopyranose-1,2-fused were cyclopropanated into compounds of type 181. After saponification with... 

Carbapentofuranoses could be obtained by periodate cleavage of an exocyclic diol in the isopropylidene protected carba hexofuranoses, as illustrated for 72. The protected carba pentofuranose 75 was obtained and deprotected to give carba- -D-lyxofuranose (76). 

The strategy for the synthesis of carba-hexofuranoses and -pentofuranoses is summarized in Scheme 16. Five new carbaanalogues of hexofuranoses were synthesized 74, 73 and the enantiomer a-L-mannofuranose, and the a-L and /3-D-glucofuranoses. The carba-analogues of the 5-deoxyhexofuranoses with a-L- and -D-lyxo-, and a-L-xyZo-configurations, which we have also prepared [98b], have recently been described, either with the same configuration, or as the enantiomeric compound, or as a racemic mixture [86]. Several of the hitherto known compounds were now obtained in a crystalline state... 

The addition of iodine trifluoroacetate (produced by reaction of iodine with silver trifluoroacetate) to unsaturated carbohydrates has been investigated.134 Treatment of 5,6-dideoxy-l,2-0-isopropylidene-a-D-xylo-hex-5-enofuranose (89) with silver trifluoroacetate and iodine in acetonitrile gave 3,6-anhydro-5-deoxy-5-iodo-l,2-0-iso-propylidene-a-D-gluco(and /3-L-ido)furanose (91) and 5-deoxy-5-iodo-l,2-0-isopropylidene-6-0-(trifluoroacetyl)-o -D-gluco(and/or /3-L-ido)-furanose (92), with the former preponderating. Component 91 was converted into 3,6-anhydro-5-deoxy-l,2-0-isopropylidene-a-D-xj/io-hexofuranose (94) by hydrogenation over Raney nickel (see also, Section III,3 p. 299), and component 92 was converted into 5-deoxy-l,2-0-isopropylidene-a-D-xy/o-hexofuranose (95) by treat-... 

An investigation of the reduction of chlorodeoxy sugars with lithium aluminum hydride has been reported.68 In one experiment, 3-deuterio-l,2 5,6-di-0-isopropylidene-a-D-allofuranose (197) was prepared, and converted into 3-chloro-3-deoxy-3-deuterio- l,2 5,6-di-0-isopropyl-idene-a-D-glucofuranose (198) by treatment with triphenylphos-phine-carbon tetrachloride reduction with lithium aluminum hydride gave 3-deoxy-3-deuterio-1,2 5,6-di-O-isopropylidene-a-D-r/foo-hexofuranose (199), a result which established that the reduction must have occurred with, retention of configuration at C-3. 

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