Aminocyclitol synthesis

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. 

Iminocyclitol, Pipecolic Acids, Homoiminocyclitols, and Aminocyclitol Synthesis... 

The aminocyclitol synthesis mediated by DHAP-dependent aldolases consists of a double aldol reaction, the first one enzymatically controlled by aldolases and the second one a spontaneous intramolecular nitro-aldol reaction (i.e., the Henry reaction) (Scheme 10.18). The latter makes use of the electrophilic carbonyl unit introduced by the first aldol addition on the nucleophilic character of carbon bonded to a nitro group installed from the acceptor (e.g., 62). This twofold C—C bond-forming reaction cascade was shown to deliver, after nitro group reduction, aminocyclitol analogs of valiolamine (63), of interest as inhibitors of intestinal glycosidases [141]. 

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...

Selective oxidation of sec -alcohols.1 The final steps in a synthesis of spec-tinomycin (3), an aminocyclitol antibiotic, involved a selective oxidation of one of three alcohol groups of 1 to provide 2, which furnishes 3 on deprotection (H2/Pd/ C, 90% yield). This oxidation can be carried out by conversion to a tributyltin ether followed by NBS oxidation to an a-hydroxy ketone in 80% yield (crude). Alternatively, reaction with Bu2SnO provides a stannylidene acetal, which is also oxidized by NBS to 2 in high yield. 

Fused ring heterocycles, prepared by cyclization of substrates with a tethered nitrogen nucleophile, have been used in the synthesis of amino sugars and aminocyclitols. The examples shown in Table 28 make use of imidate-type functionality (equation 101) to insure nucleophilic attack by nitrogen. The bro-mocyclization of N,W-dialkylaminomethyl ethers of 2-cyclohexen-l-ol to form bicyclic oxazolidine derivatives has been reported also.228b... 

Feng, X., Duesler, E.N., and Mariano, P.S. (2005) Pyridinium salt photochemistry in a concise route for synthesis of the trehazolin aminocyclitol, trehazolamine. Journal of Organic Chemistry, 70 (14), 5618-5623. 

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. 

Y. Kobayashi, H. Miyazaki, and M. Shiozaki, Synthesis and absolute configuration of trehazolin aminocyclitol moiety, Tetrahedron Lett., 34 (1993) 1505-1506. 

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. 

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