Trehalosamine

Trehalosamine, 2-amino-2-deoxy-a-D-glucopyranosyl a-D-glucopy-ranoside (343), is an antibiotic produced by Streptomyces tavendulae. Four related compounds, the 3-amino-3-deoxy and 4-amino-4-deoxy isomers," ... 

Coupling of 237 with the protected 2-amino-2-deoxy-o -D-glucopyranosyl bromide (348) in dichloromethane in the presence of silver triflate afforded a diastereoisomeric mixture. The isomer related to the natural one was depro-tected with sodium in liquid ammonia, to give the carba-trehalosamine... 

Carba-trehalosamine was found to show 25% of the activity of 2-treha-losamine, which showed that, in biologically active oligosaccharides, re-... 

Such carba-disaccharides as validoxylamines A and B were synthesized as intermediary compounds in the total synthesis of validamycin antibiotics. Carba-disaccharides related to maltose, isomaltose, cellobiose, the trehaloses, and trehalosamine modifications have also been synthesized. 

The remarkably successful clinical application of aminoglycoside antibiotics attracted the attention of many organic chemists. With his continuous interest in this field for more than 20 years, Sumio Umezawa accomplished the first total synthesis of many aminoglycosides, including paromamine,- neamine," trehalosamine, kanamycins A, B, and C, 2 butirosin B, tobramycin, " streptomycin, dihydrostreptomycin, and neomycins B and C. ... 

Trehalosamines are representative of the disaccharides in this class of aminoglycosides and are relatively weak antihiotics. Trehalosamine (compound 118) [117], its 2-epimer maimosylglucosaminide [118], and the 4-amino derivative compound 119 [119] were isolated from culture filtrate of Streptomyces and showed weak an-... 

Trehalosamine (433), an a,a-(l l)-linked disaccharide produced by Streptomyces lavendulae, is an aminoglycoside antibiotic composed of D-glucose and 2-amino-2-deoxy-D-glucose [252],... 

O. Ando, M. Nakajima, K. Hamano, K. Itoi, S. Takahashi, Y. Takamatsu, A. Sato, R. Enokita, T. Okazaki, H. Haruyama, and T. Kinoshita, Isolation of trehalosamine, the aglycon of trehazolin, from microbial broths and characterization of trehazolin related compounds, J. Antibiot., 46 (1993) 1116-1125. 

The presence of trehalase in the tubercle bacillus was discovered by Bloch and SuUman in 1945. Optimal hydrolysis of a,a-trehalose by the enzyme occurred in acid to neutral solutions. Since a,a-trehalose is not utilized by the bacteria so rapidly as is n-glucose, it was inferred that the bacillus only metabolizes the a, -trehalose after the trehalase has converted it into D-glucose. Trehalosamine (see p. 220) has an antimycobac-terial effect. This effect is antagonized by a,a-trehalose. One mole of trehalosamine as inhibitor removes 0.337 mole of Q ,a-trehalose from the surface of the enzyme. Total inhibition of mycobacterial trehalase is not readily produced. Cord factor was also isolated from wax D of a BCG strain of M. tuberculosis in 1959 by Nojima. A list of fatty acid esters of a, a-trehalose is given in Table I. 

Miscellaneous Chemical Types Kasugamycin, Spectinomycin, a,o-Trehalosamine and a-n-Mannosyl 2-Amino-2-deoxy-aH -glucoside, Validamycins, and Apramycin... 

These antibiotics are nonreducing disaccharides. The chemistry of a,a-trehalosamine (69) has been reviewed, and the compound has been synthesized (see p. 153). 

Yonehara and coworkers isolated a-n-mannosyl 2-amino-2-deoxy- -D-glucoside (70), which is coproduced with a,o-trehalosamine by Strepto-... 

Paromamine, neamine, 4-0-(6-amino-6-deoxy- -D-glucopyranosyI)-2-deoxystreptamine, 5-0- (2-amino-2-deoxy-o-D-glucopyranosyl) -2-deoxy-streptamine, kasugamycin, and a,a-trehalosamine have been synthesized. A common feature in the structures of these antibiotics is the presence of an a-o-glycosidic linkage. In the total syntheses, modified Koenigs-Knorr reactions, or addition of nitrosyl chloride " to an enose, were successfully used. 

A Streptomyces spedes has been shown by Arcamone and Bizioli to produce 2-amino-2-deoxy-a-D-glucopyianosyl a-n-glucopyranoside (a,a-trehalosamine), and to excrete this amino disaccharide into the culture medium. Interestingly, this compound exhibits antibiotic activity against mycobacteria, probably because it is a competitive inhibitor of die trehalase. ... 

Considerable attention has been given to amino-sugar disaccharides. The 2-azido-2-deoxyglycosyl chloride procedure has been applied to obtain 2-amino-2-deoxy-a-D-glucopyranosyl a-D-glucopyranoside (trehalosamine)/ and the 2-deoxy-2-phthalamidoglycosyl bromide method to produce 6-0-(2-acetamido-... 

C -Acetyl-2-azido-3,4-di-0-benzyl-2-deoxy-j3-D-glucopyranosyl chloride reacts with 2,3,4,6-tetra-0-benzyl-o -D-glucopyranose or 2,3,4,6-tetra-O-acetyl-a-D-mannopyranose with good stereoselectivity to yield Q ,a-trehalosamine or 0 ,a-mannotrehalosamine (Scheme 2) Several other 0 ,tt-(l l)-linked disaccharides of the trehalosamine type and containing additional azido-groups were also synthesized. 

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