Synthesis of Aminocyclitols

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. 

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. 

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... 

L. El Blidi, Z. Assaf, F.C. Bres, H. Veschambre, V. Thery, 1. Bolte, M. Lemaire, Fmctose-1,6-bisphosphate aldolase-mediated synthesis of aminocyclitols (analogues of valiolamine) and their evaluation as glycosidase inhibitors, Chem. Catal. Chem. 1 (2009) 463-471. 

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. 

Y. Kobayashi, H. Miyazaki, and M. Shiozaki, Synthesis of trehazolin, trehalamine, and the aminocyclitol moiety of trehazolin Determination of absolute configuration of trehazolin, J. Org. Chem., 59 (1994) 813-822. 

C. Uchida, H. Kitahashi, T. Yamagishi, Y. Iwaisaki, and S. Ogawa, Synthesis of trehazolin analogues containing modified aminocyclitol moieties, J. Chem. Soc. Perkin Trans., 1 (1994) 2775-2785. 

M. Akiyama, T. Awamura, K. Kimura, Y. Hosomi, A. Kobayashi, K. Tsuji, A. Kuboki, and S. Ohira, Stereocontrolled synthesis of the aminocyclitol moiety of (+)-trehazolin via C-H insertion reaction of alkylidenecarbene, Tetrahedron Lett., 45 (2004) 7133-7136. 

These transformations have been used for a synthesis of the aminocyclitol sporamine (4). 

Nakata, M, Akazawa, S, Kitamura, S, Tatsuta, K, Enantiospecific total synthesis of (—)allosazoline, an aminocyclitol moiety of the insect chitinase inhibitor allosamidin. Tetrahedron Lett., 32, 5363-5366, 1991. 

Also, Ogawa s group reported the s)mthesis of racemic trehazolin aminocyclitol derivatives, as well as trehazolin and its diastereoisomers from wtyo-inositol, and thus contributed independently to the determination of the correct stereochemistry of trehazolin [182,183,184,185,186]. The successful total synthesis of trehazolin (223) encouraged Kobayashi and Shiozaki et al. to investigate stmcture-activity relationships regarding the inhibitory activities towards vari-... 

Moreover, these authors prepared the aminocyclitol 226 needed for the synthesis of trehazolin (223) from the allyl alcohol 269a. Epoxidation of 269a with mCPBA gave the desired epoxide 276 exclusively. The epoxide 276 was exposed to 2 1 H2O-TFA to open the epoxy ring, and afforded the alcohols 277. They were transformed to peracetates 278a and 278b,... 

A synthesis of spectinomycin together with the preparation of its 5 -n-butyl analog (replacement of the methyl group with n-butyl group) has been described. The 5 -n-butyl derivative (trospectomycin or 6 -n-propylspectinomycin) showed potent antibacterial activity and is the only aminocyclitol antibiotic that is active against anaerobic bacteria [182]. 

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