Streptamines

The term aminogl)icosi(k is commonly used to refer to members of the class of antibacterial antibiotics, the stmctures of which ate derived from D-streptamine [488-52-8] (1, R = OH), D-2-deoxystreptamine [2037-48-1] (1, R = H), or closely related compounds. The terms... 

Perhaps the greatest utility of (36-39) (and many of their precursors, such as 41, 42 and 48) is as starting points for the synthesis of highly functionalized cyclohexanes. For example, (38) has been converted in five steps (overall yield 70-75%) to streptamine (57) the key step is selective ring-opening with hydrazine to give intermediate (56) (75AG(E)630). 

Chemical Name (S)-0-3-amino-3-deoxy-a-D-glucopyranosyl-(1->6)-0-(6-amino-6-deoxy-a-D-glucopyranosyl-(1->4)] -N -(4-amino-2-hydroxy-1-oxobutyl)-2-deoxy-D-streptamine... 

Chemical Name D-Streptamine, 0-3-amlno-3-deoxy-0t-D-glucopyranosyl-(1- 6)-O-[2,6-dl-amino-2,6-dideoxy-0t-D-glucopyranosyl-(1 4)]-2-deoxy sulfate (1 1)... 

Chemical Name 0-3-Amino-3-deoxy-o -D-glucopyranosyl-(1-> 6)-0-[2,6-dlamino-2,3,4,6-tetradeoxy-o -D-erythrohexopyranosyl(1" 4)] -2-deoxy-D-streptamine... 

Chemical Name 0-2-Deoxy-2-(methylamino)-a-L-glucopyranosyl-(1 2)-0-5-deoxy-3-C-(hydroxymethyl)-a-L-lyxofuranosyl-(1 4)-N,N -bis(aminoiminomethyl)-D-streptamine... 

The obvious solution is to feed these cells with compounds that have structures similar to 2-deoxystreptamine, which would become incorporated into the neomycin. If for example, streptamine is included in the fermentation broth, this is incorporated into the neomycin produced. Thus ... 

RN 119-04-0 MF C23H46N6OB MW 614.65 EINECS 204-292-2 CN 6>-2,6-diamino-2,6-dideoxy-a-D-gIucopyranosyI(l->4)-0-[0-2,6-diamino-2,6-dideoxy-p-L-idopyranosyl-(l->3)-P-D-ribofuranosyl-(l->5)]-2-deoxy-D-streptamine... 

Simple analogs of an aminoglycoside antibiotic, 2,6-dideoxy-4-0- (671) and -5-0-(2,3-dideoxy-2-fluoro-o -D-r/Z>o-hexopyranosyl)streptamine (672) were prepared by coupling of tri-O-acetyl-2-fluoro-D-glucal (666) with cyclitol derivatives 668 or 667 (through 669 and 670) as shown. 

D-glucopyranosyl- (l->4) -0- [0-02, 6-diamino-2,6-dideoxy-3 L-o idopyranosy 1- (1+3) - 8-D-ribo-furanosyl-c (1+5)] -2-deoxy-D-streptamine. 

Fig. 7 Schematic representation of the conformational differences (highlighted with a dotted box) exhibited by aminoglycosides in the binding pockets of RNA (a) and some of the enzymes involved in bacterial resistance (b). The glucose, 2-deoxy-streptamine and ribose units are numbered as I, II and III respectively...

Other medicinally useful aminoglycoside antibiotics are based on the aminocyclitol 2-deoxystrepta-mine, e.g. gentamicin Ci from Micromonospora purpurea. Although streptamine and 2-deoxystrepta-mine are actually cyclohexane derivatives, they are both of carbohydrate origin and derived naturally from glucose. 

---