Of aminocyclitol

Beside AAC enzymes two different enzyme classes, nucleotidyltransferases (ANT enzymes), and phosphotransferases (APH enzymes) modify the hydroxyl groups of aminocyclitol-aminoglycoside antibiotics. 

Figure 10.27 Preparation of aminocyclitol precursors by chemoenzymatic tandem reactions.

Lemaire et al. have developed a efficient fructose-1,6-bisphosphate aldolase (FBPA)-mediated synthesis of aminocyclitol analogs of valiolamine [34], This one-pot route involves the formation of two C—C bonds where four stereocenters are created. The first C—C bond formation reaction is catalyzed by the aldolase, coupling DHAP to nitrobutyraldehydes the other one is the result of a highly stereoselective intramolecular Henry reaction occurring on the intermediate nitroketone under acidic conditions during the aldolase-catalyzed reaction and phytase-catalyzed phosphate hydrolysis coupled step (Scheme 4.13). 

Scheme 4.13 Multi-enzyme route for the synthesis of aminocyclitol analogs of valiolamine...

S. Ogawa, C. Uchida, and Y. Yuming, Synthesis of aminocyclitol moieties of trehalase inhibitors, trehalostatin and trehazolin, J. Chem. Soc. Chem. Commun. (1992) 886-888. 

J. Marco-Contelles, P. Gallego, M. Rodriguez-Femandez, N. Khiar, C. Destabel, M. Bemanbe, A. Marinez-Grau, and J. L. Chiara, Synthesis of aminocyclitols by intramolecular reductive coupling of carbohydrate derived <5- and 8-functionalized oxime ethers promoted by tributyltin hydride or samarium diiodide,./. Org. Chem., 62 (1997) 7397-7412. 

Instead of describing the biosynthesis of the individual sugar components of these antibiotics, it is advantageous to review the biosynthesis of the total molecule. A review on the biosynthesis of aminocyclitol ( aminoglycoside ) antibiotics has appeared.47... 

Alkali metal in ammonia reductions of pyrrolobenzodiazepine-5,11-diones give trans-2-aminocyclohexanecarboxylic acid derivatives (e.g., 4) in enantiomerically pure form.2 3 A method for preparation of cis-2-aminocyclohexanecarboxylic acids related to 4 is based on the enantioselective hydrolysis of symmetrical diesters with pig liver esterase.4 cis-2-Aminocyclohexane derivatives have been used for syntheses of aminocyclitol antibiotics.4 5 6-Alkyl-cis-2-aminocyclohexanecarboxylic acids can be prepared by alkali metal in ammonia reduction of pyrrolobenzodiazepine-5,11-diones followed by olefin hydrogenation the cis-decahydroquinoline alkaloid (+)-pumiliotoxin C has been prepared by this methodology.2... 

Walker, J.B., 1995, Enzymatic synthesis of aminocyclitol moieties of aminoglycoside antibiotics from inositol by Streptomyces spp. Detection of glutamine-aminocyclitol aminotransferase and diaminocyclitol aminotransferase activities in a spectinomycin producer. J. Bacteriol. 177 818-822. 

P. Hu, E.K. Chess, S. Brynjelsen, G. Jabubowski, J. Melchert, R.B. Hammond, T.D. Wilson, CID of aminocyclitol-aminoglycoside antibiotics and their application in the identification of a new compound in tobramycin samples, J. Am. Soc. Mass Spectrom.,... 

In a review on the biosynthesis of aminocyclitols it was pointed out that glucose generally supplied the carbon backbone of each moiety.17 Mutants of S. fradiae and S. rimosus incorporated 2,6-dideoxystreptamine into 6-deoxyneomycins and 6-deoxyparomomycins, respectively.18... 

It should be noted that the addition of aminocyclitol derivatives to glycals catalyzed by boron trifluoride etherate also affords l,2-d5 -aminoglycosides stereo-selectively. Thus, the glycosyl product 54 with an a-anomeric linkage was obtained in 65% yield by addition of the alcohol 53 to the glycal 35 [48] (compounds 53, 54). 

T. Posternak, Studies on cyclitols XIV. Nitrous deamination of aminocyclitols. Synthesis of d, 1-vibumitol and new total synthesis of meso-inositol, Helv. Chim. Acta, 33 (1950) 1597-1604. 

A comprehensive review on the biosynthesis of aminocyclitol antibiotics was published by K. L. Rinehart and R. M. Stroshane Most of the biosynthetic studies have been directed to the largest and most important group, the deoxystreptamine-containing antibiotics. The biosynthesis was followed by C-or C-isotope labelling of subunits and determination of the level of activity in isolated intermediates and in final products by degradation, NMR-spectroscopy and mass spectrometry. 

The Suami and Ogawa group has been particularly active in the field of carbocyclic polyols. The main line of their interest was confined to the synthesis of aminocyclitols, constituents of aminoglycoside antibiotics and their analogs. Besides, inosamines and aminocyclopentanepolyols obtained in their laboratory were utilized as substrates in synthesis of nucleoside analogs. A... 

This procedure introduced by Ferrier, involving the mercury salt-mediated ring transformation of 6-deoxyhex-5-enopyranosides into deoxyinososes, has provided a route of wide practical utilization in the field of aminocyclitols [42 6] and pseudo-sugar chemistry [47, 48]. This procedure has led to the preparation [49] of the B-A ring system of the antibiotic b-rhodomycin and has extended [50] to thioglycoside analogs of hex-5-enopyranosides (Fig. 8.29). 

L-C iinic acid has been converted to the trihydroxycyclohexanone derivative (22), which was then used to synthesize a range of aminocyclitols including 2,6-dideoxystreptamine (23),2,5,6-trideoxystreptamine, 5-amino-2,5,6-trideoxy-streptamine, and 3,5-dideoxyfortamine (24), by standard transformations, especially sulphonate -> azide sequences. ... 

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