Glucosamine isomers

The isomeric pentacetates of glucosamine were prepared as long ago as 1899 by Lobry de Bruyn and van Ekenstein85 and the proportions of the o-and /3-isomers obtained with various reagents are shown below in Table II. 

The synthesis of this substance, starting with methyl 2-acetamido-4,6-0-benzylidene-2-deoxy-a-D-glucoside, was performed as follows. The two isomers which were formed were separated on a Dowex 50 colunm, and one (Md +109°) was shown to be identical with natural muramic acid. The strong dextrorotation effectively ruled out the L-glucosamine configuration, and the configuration of the lactic moiety was deduced to be most likely d. The second isomer had [ ] +52° and differed, in its behavior on resin columns and in paper chromatography, from natural muramic acid. 

The highly levorotatory y-hexaacetate would have to be a structural isomer of the two anomeric a and /3 hexaacetates. It was pointed out that the aldehyde structure XLIII was improbable from the mode of its formation moreover it was excluded by the fact that the compound failed to give rise, on treatment with thiosemicarbazide, to the ultraviolet absorption band at 2700 A characteristic of tiuosemicarbazones. Since ring isomerism in the N-methyl-L-glucosamine portion or a 1,3-orthoacetate structure did not seem probable, the 1,6-furanose structure (XLIV) was tentatively proposed for this compound. 

Synthesis from o-glucosamine The first asymmetric syntheses of (-)-rosmari-necine (20) and (-)-7-deoxyrosmarinecine (118) have been carried out using the carbamate 108, " prepared from methyl a-D-glucosaminide (Schemes 6 and 7). ° Silylation of 108 with TBSCl followed by condensation with allylmagnesium bromide afforded the threo isomer 109. The R configuration of the newly formed asymmetric carbon atom was rationalized by a chelation-controlled approach. - Oxidation of the olefin 109 with sodium... 

A convenient means of preparing L-glucosamine has been published which proceeds by ascent of the series from L-arabinose (BnNH2-HCN). The required L-glucosamine is separated from the L-manno-isomer by conversion to its crystalline Schiff base, formed from 4-methoxybenzaldehyde. ... 

In a new formal synthesis of (-h)-thienamycin (Scheme 29), the 6-deoxy-glucosamine derivative 142 underwent base-catalysed rearrangement (see Vol. 16, p. 149), followed by oxidation, to give the separable isomers of 143. Both of these could be transformed, by sequences involving base-catalysed epimeriz-ation, into the same all-frans-lactone 144. Formation of a p-lactam and then oxidation by lead tetraacetate gave 145 (original sugar carbons indicated), which is an intermediate in a previous route to thienamycin. ... 

Cyclization of 5,6-dideoxv-6-nitro-D-xylo-hexofuranose led to a mixture of myo- and epi-isomers (43) which were separated and converted to the corresponding amino compounds.Examples of the use of the Ferrier reaction for preparing cyclitols and amino-cyclitols from D-glucose and D-glucosamine have been published, e.g., (44)- (45).52... 

In the synthesis of N-acetyl-muramyl-peptides, and obviously of MDP, the most frequently used protected muramyl derivative is 1-O-benzyl-4,6-O-benzylidene-N-acetyl-muramic acid. This allows the mild and possibly simultaneous elimination of the benzylidene group and the benzyl group. Starting from D-glucosamine, either a- or p-benzyl-4,6-0-benzylidene-N-acetyl-muramide can be obtained (Fig. 4) 17, 25, 53). In spite of its slower hydrogenolysis rate 44), the a-isomer which is easier to prepare is generally preferred (55, 44) to the p-isomer 50). 

The synthesis of N-acetyl-P-D-glucosaminyl-(l- 4)-N-acetyl-mur-amyl-dipeptide according to various synthetic (82—84) and hemi-synthetic (85) procedures has been described, and, also, the synthesis of one of its isomers 0-(N-acetyl-P-muramyl-L-alanyl-D-isoglutamine)-(l- 4)-N-acetyl-D-glucosamine (90) (86). 

The direct synthesis of trisaccharides has also been realized using the standard reagent combination. Thus, treatment of the glucosamine donor 16 with BSP/Tf20/TTBP at —60°C in dichloromethane, followed by addition of 4,6-glucopyranosyl diol (17) furnished the trisaccharide 18 in 85% yield as a single isomer (eq 6) ... 

Two forms of glucosamine hydrochloride have been described, one the common a-D-isomer with [ ]d+100°+72.5 , and the other the iS-D-isomer with [a]n +25.0° +72.6°, in water (285). Salts of other acids... 

---