Hexoses , preparation

The crystalline tri-0-isopropylidene-(2-hydroxy-L-x2/Zo-hexose) prepared from L-gulosone closely resembles the corresponding o-arabino-hexose derivative7 (p. 73) and is believed to have a similar structure.193 On graded hydrolysis, it forms a di-O-isopropylidene derivative which may be characterized as the crystalline diacetate. 

Besides the D-glucose derivative just described, three other crystalline dichlorides have been prepared from 2-hydroxyglycals, namely, the dichlorides from 2,3,4,6-tetra-0-benzoyl-(2-hydroxy-D-glucal)10 (yield, 22%), 2,3,6,2, 3, 4, 6,-hepta-0-acetyl-(2-hydroxycellobial)IS (yield, 30%), and 2,3,4-tri-0-benzoyl-(2-hydroxy-D-xylal)12 (yield, 17%). The 2,3,4,6-tetra-0-benzoyl-l,2-dichloro-l-deoxy-D-hexose prepared from the first of these by short chlorination in benzene reacted with sodium acetate in hot, glacial acetic acid. The crystalline product was assigned the structure of l-0-acetyl-3,4,6-tri-0-benzoyl-D-glucosone10 since it is not converted to kojic acid by pyridine-acetic anhydride (see below). A benzoyl group has been lost. 

Pratt, J W, Richtmyer, N K, Crystalline 3-deoxy-a-D-nho-hexose. Preparation and properties of 1,6-anhydro-3-deoxy-a-D-arafa>io-hexopyranose, 1,6-anhydro-3-deoxy-p-D-n ho-hexopyranose and related compounds, J. Am. Chem. Soc., 79, 2597-2600, 1957. 

Would either of these reactions offer an advantage over the other in the preparation of hexoses for entry into glycolysis ... 

Sharpless and Masumune have applied the AE reaction on chiral allylic alcohols to prepare all 8 of the L-hexoses. ° AE reaction on allylic alcohol 52 provides the epoxy alcohol 53 in 92% yield and in >95% ee. Base catalyze Payne rearrangement followed by ring opening with phenyl thiolate provides diol 54. Protection of the diol is followed by oxidation of the sulfide to the sulfoxide via m-CPBA, Pummerer rearrangement to give the gm-acetoxy sulfide intermediate and finally reduction using Dibal to yield the desired aldehyde 56. Homer-Emmons olefination followed by reduction sets up the second substrate for the AE reaction. The AE reaction on optically active 57 is reagent... 

In extending this direct method of synthesis, we next investigated the possibility of preparing similarly constituted halides from 2-deoxy-D-arabino-hexose (2-deoxy-D-glucose) (21). The hexose was subjected to a partial anomerization procedure described by Bergmann and co-workers (1). The solid material obtained by this procedure is a mixture of the anomeric forms of 2-deoxy-D-arabino-hexose low temperature p-nitro-benzoylation of the latter in pyridine resulted in a mixture of crystalline, anomeric tetrakis-p-nitrobenzoates in a ratio of approximately 1 1. They were readily separable by fractional recrystallization, and treatment of either with an excess of hydrogen bromide in dichloromethane, or with... 

The bromide (5) failed to couple with dialkoxypyrimidines, even at elevated temperatures the failure is probably because of steric conditions imposed by the axially oriented C-4 p-nitrobenzoyloxyl group (see structure 5) this same group in the other halides (la, lb, 2a, 2b, 4a, and 4b) discussed in the foregoing is an equatorial substituent. Accordingly, the preparation of a differently constituted halide of 2-deoxy-D-Zt/xo-hexose is being investigated for the synthesis of pyrimidine nucleosides. 

The first known pseudo-hexose, pseudo-a-DL-toZopyranose (34) was prepared by reduction of the keto-acid monoacetate (30) 26, 27). This intermediate, which had been used by Daniels, Doshi, and Smissman (9, JO) for a synthesis of shikimic acid, is prepared from the Diels-Alder adduct (31) of 2-acetoxyfuran and maleic anhydride, by a remarkable series of transformations. 

Deoxy-D-jcylo hexose 6-(dihydrogen phosphate) (21) has also been synthesized (2) the reaction sequence makes use of 3-deoxy l 2,5 6-di-O-isopropylidene D-galactofuranose (16), a compound that can be easily prepared from D-glucose (2, 60). The mono-isopropylidene derivative (17) formed by partial hydrolysis of the di-ketal is converted into the 6-tosylate (18) by reaction with one molar equivalent of p-toluenesulfonyl chloride. From this the epoxide (19) is formed by reaction with sodium methoxide. Treatment of the anhydro sugar with an aqueous solution of disodium hydrogen phosphate (26) leads to the 6-phosphate (20)... 

A mixture of d- and l- hexoses also results from the hydroboration of these 5-enes. Hydroboration results in anti-Markownikoff, cw-hydration of the double bond and the amount of each hexose formed varies according to the nature of the substituent groups. For example, hydroboration (23) of methyl 6-deoxy-a-D-ryZo-hex-5-enopyranose (3) affords methyl a-D-glucopyranoside and methyl / -L-idopyranoside in the ratio of 1 2.5 respectively whereas hydroboration of the fris-trimethylsilyl ether of 3 afforded them in the ratio 1 0.6 respectively. The hydroboration method can be used to achieve specific labelling of hexoses with tritium methyl-/ -L-idopyranoside[5-H3] and methyl a-D-glucopyranoside [5-H3] were thus prepared (23). Similarly, hydroboration of the D-Zt/ro-hex-5-eno derivative (14) with diborane-H3 followed by removal of the isopropyli-dene group, afforded methyl a-D-mannopyranoside [5-H3] and methyl / -L-gulopyranoside [5-H3] in the ratio of 1 2 respectively (23). 

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... 

Crystalline phosphoric acid has also been used to prepare sugar diphosphates, e.g. a-D-ribose 1,5-diphosphate (62) and hexose 1,6-diphosphates. 

Intramolecular cycloadditions of chiral nitrones provide a useful tool for the preparation of bioactive heterocyclic compounds.63 Shing et al. demonstrated that 1,3-dipolar cycloaddition of nitrones derived from 3-0-allyl-hexoses is dependent only on the relative configuration at C-2,3, as shown in Scheme 8.16. Thus 3-0-allyl-D-glucose and -D-altrose (both with threo-configuration at C-2,3) produce oxepanes selectively, whereas 3-O-allyl-D-allose and -D-man-nose (both with erythro-configuration at C-2,3) give tetrahydropyranes selectively.80... 

The best known 2,5-anhydro hexose is that which was prepared in 1894 by Fischer and Tiemann4 and named by them chitose. Chitose is a liquid with ill-defined properties and is usually characterized by its oxidation derivatives, chitonic acid and isosaccharic acid. It is prepared by the deamination of the naturally occurring chitosamine (D-glu-cosamine). 

VI. Anhydro Sugars of the Glycosan Type 1. Preparative Methods for 1,6-Anhydro Hexoses... 

A similar series of reactions applied to L-sorbose (once a rare sugar but now easily obtained from sorbitol by bacterial oxidation16) gives rise to 2-keto-L-gulonic acid.4 The method is not confined to keto-hexoses and has been employed in the preparation from L-erythropentulose (XXXI) of the 2-keto-L-ribonic acid (XXXV) which undergoes immediate transformation to the corresponding L-erythroascorbic acid (XXXVI).16... 

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