N-Methyl-L-glucosamine

Streptomyces Antibiotics. XV. N-Methyl-L-glucosamine. J. Amer. chem. Soc. 69, 3032 (1947). 

It was pointed out that N-methyl-L-glucosaminic acid nitrile was only the second nitrile in the sugar series to be isolated in the cyanohydrin reaction and that extension of the general procedure by which it was prepared should result in the isolation of other members. The nitrile of N-methyl-L-glucosaminic acid showed the same unusual mutarotation as does that of the lower-melting form of D-gluconic acid nitrile. Wolfrom and Thompson have noted that N-methyl-L-glucosaminic acid nitrile hydrochloride was a much more stable compound than the free base. 

In the preparation of N-methyl-L-glucosaminic acid nitrile by treatment of an ethanol solution of N-methyl-L-arabinosylamine with hydrogen cyanide, it was to be expected that the epimeric N-methyl-L-man-nosaminic acid nitrile Avould also be formed. Wolfrom and Thompson" were able to isolate in crystalline condition the acetylated nitrile of N-methyl-L-mannosaminic acid from this reaction mixture. This compound was converted to crystalline N-methyl-L-mannosaminic acid. 

The reduction of N-methyl-L-glucosaminic acid lactone with sodium amalgam in sulfuric acid led to crystalline pentaacetyl-N-methyl-a-L-glucosamine" from which crystalline N-methyl-L-glucosamine (free base) was prepared." Pentaacetyl-N-methyl-/8-L-glucosamine and N-acetyl-N-methyl-L-glucosamine were also isolated. 

Hydrogenation of the crystalline streptomycin trihydrochloride-calcium chloride double salt in aqueous solution with platinum oxide catalyst at atmospheric pressure or with Raney nickel catalyst at 100-140 atmospheres and 150° also yielded dihydrostreptomycin. Acid hydrolysis of dihydrostreptomycin gave streptidine and N-methyl-L-glucosamine. Hence, the reduction involved the nitrogen-free moiety, streptose. 

Hydrolysis of pentaacetylstreptobiosamic acid monolactone in refluxing 2.5 N hydrochloric acid yielded a crystalline compound derived from the streptose moiety. This compound was designated streptosonic acid monolactone and was further characterized as its diacetate. The hydrolyzate was shown to contain N-methyl-L-glucosamine. 

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. 

An Improved Synthesis of N-Methyl-L-glucosaminic Acid, M. L. Wolform, Alva Thompson, and I. R. Hooper, Science, 104, 276-277 (1946). 

Derivatives of N-Methyl-L-glucosaminic Acid N-Methyl-L-mannosaminic Acid, M. L. Wolfrom and Alva Thompson, 7- Amer. Chem. Soc., 69, 1847-1849 (1947). 

Hitose-Kumagai A, Yagiia A. Akamatsu N. tlDP-N-mcthyl-D-glucosamine-phosphatc. A possible intermediate of N-methyl-L-glucosamine moiety of str omycin. J Antibiot 1982 35 1571-1577. 

The biosynthesis of the N-methyl-L-glucosamine moiety of streptomycin from D-glucosamine by S.griseus has been studied. Addition of thymine to the culture medium stimulated formation of streptomycin, and the conversion of D-glucosamine to N-methyl-L-glucosamine. A novel UDP-aminosugar nucleotide intermediate,... 

N-methyl-L-glucosamine (N methyl-2-amino-2-deoxy-L-glucopyranose). 

Kuehl etal., 1947 Wolfrom et al., 1950 Dyer et al., 1965) The glycosidic bonds between the moieties are a-L in configuration (Wolfrom et al., 1954 McGilveray et aL, 1965). Mild acid hydrolysis results in the fission of the glycosidic bond between the streptidine and streptose moieties. The products of mild acid hydrolysis are streptidine and a disaccharide designated streptobiosamine which is composed of streptose and N-methyl-L-glucosamine. [For reviews on the determination of structure see (Lemieux and Wolfrom, 1948 Brink and Folkers, 1949, 1950)]. 

The carbon 1 of the D-mannose is joined by glycosidic linkage to carbon 4 of the N-methyl-L-glucosamine moiety of streptomycin (Fried and Stavely, 1947, 1952). It is usually found to some extent in streptomycin-producing cultures of... 

---