Amino sugars cyclizations

In carbohydrate chemistry, the most described method for the preparation of saccharidic thionocarbamates involves preliminary introduction of the amine function on a partially or non-protected saccharidic template. The condensation of amino sugars with carbon disulfide or thiophosgene leads to cyclization in 1,3-oxazolidine- or l,3-oxazine-2-thiones. This reaction involves the formation of an intermediate isothiocyanate, which reacts further with a 3- or y-located hydroxyl group. The viability and facility of this process depends on the saccharidic ring size and the inherent strain. Some major rules can be put into light from the cases studied 30... 

Piperidines are obtained from 5-amino-5-deoxy sugars by cycliza-tion with C-l their preparation therefore follows the general methods of preparation of such amino sugars. The 5-O-p-tolylsulfonyl- or 5-0-(methylsulfonyl)-pentoses constitute excellent starting-materials, as these sulfonyloxy groups can be replaced by azide, and the azides can be reduced to the 5-amino derivatives, which are capable of cyclization.240-251 The formation of piperidine 178 from 5-O-p-tolyI-sulfonyl-L-arabinose diethyl dithioacetal240 (176) and 177, and of 181 from benzyl 2,3-0-isopropylidene-5-0-(methylsulfonyl)-a-D-lyxofuranoside250 (179) and 180, are examples of this reaction sequence. 

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... 

Cyclization of the bis-epoxides 123 (mixtures of diastereomers) with benzylamine afforded the azepanes 124 in a preferential 1-endo-tet methodology (Equation 17) <1995JOC5958> however, with the corresponding 3,4-benzyl ethers of the bis-epoxides rather than the // / -acetonide protecting group, no cyclization to six-membered ting species was observed. The azepanes 124 were then converted in two steps to the amino sugar hydrochloride salts 126 via the N-debenzylated intermediates 125 (Scheme 16). 

Three inosamines were obtained in the course of efforts to synthesize myo-inositol by the nitro-sugar cyclization (see p. 142). However, the methods which have been the most productive of new inosamines are those which are well known as means of preparing amino sugars and aminopolyhydric alcohols, namely, reduction of imine derivatives of carbonyl compounds (in this case, inososes) and ammonolysis of halohydrins and epoxides. 

This protocol led to the diamine 46, which also represents a protected amino sugar (2,4-diamino-2,4-dideoxy-L-xylose). Interestingly, the direct reductive amination of 47 was followed by in situ cyclization to afford the lactam 48 as the major diastereomer. 

Aldol-type cyclization of dialdehydes with nitroalkanes is a valuatde syndietic loute to amino sugars, amino cyclitols and nucleosides of amino sugars. Recently, die cyclization of die di- and tetra- de-hydes derived from sucrose (15) with nitroalkanes has appeared. It is notewordiy that the oxidadve cleavage of sucrose with LTA affords the dialdehyde selectively (Scheme 8). ... 

One other example of an intramolecular -sulfinyl carbamate cycloaddition is depicted in Scheme 17. In this case, diene carbamate (133) was converted to a sulfinyl compound which cyclized to give exclusively adduct (135). It was suggested that the cycloaddition occurs via an endo boat-like iV-sulfinyl carbamate conformation (134). The alternate endo chair-like conformation (137) leading to isomeric adduct (138) is destabilized relative to (134) due to an eclipsing interaction between Ha and Hb. Adduct (135) was converted to amino sugar (136) in a few steps. 

The traditional method for preparing oxazolidines is to heat a mixture of amino alcohol and aldehyde in a solvent such as benzene with removal of water. A milder procedure that affords some products in high yield when they would otherwise be obtained in only trace amounts is to dehydrate the same mixture with molecular sieves in methylene chloride at room temperature <89JHC1687>. A method that has been effective with amino sugar derivatives is to cyclize with dibromomethane under phase transfer conditions <93Mi 304-02>. 

Five- and six-membered rings have also been formed by participation of the amino groups of amino sugars in intramolecular displacements. Thus, hydrogenation of the azido compound (256) gave the pyrrolidine (258) clearly, the intermediate amino sugar derivative (257) cyclizes... 

Several 4-deoxy-4-nitro ketose derivatives have been synthesized. Three crystalline 2,7-anhydro-4-deoxy-4-nitro-/3-D-heptulopyranoses arose by nitromethane cyclization92 of the dialdehyde (74) produced by periodate oxidation of sedoheptulosan (73), and were assigned93 the D-alio (75), D-gulo (76), and D-altro (77) configurations by nuclear magnetic resonance spectroscopy of the corresponding, peracetylated amino sugars. When the cyclization of 74 was performed in methan-olic medium, a solid mixture of stereoisomeric nitronates was obtained in almost quantitative yield, and it could be partially separated into the individual nitronates, which furnished 75 and 76. The isomer 77... 

The key step here involved cycloaddition of the Af-sulfinyl carbamate 30 to give exclusively adduct 31, whose structure was proved by X-ray crystallography. It was suggested that the cyclization occurred via the con-former shown in 30 to minimize nonbonded interactions. It seems reasonable that the reaction proceeded through an intermediate ( )-Af-sulfinyl carbamate to provide the sulfur stereochemistry shown in structure 31. This cycloadduct was subsequently converted to the amino sugar by a short series of transformations. 

Ureas prepared from primary allylic amines slowly decomposed under the conditions listed without providing any cyclized products. Furthermore, the synthesis of amino sugars by the IBX-mediated cyclization protocol was also accomplished. This method was found to be stereoselective. A few examples are listed below ... 

Shiori and co-workers used 5-substituted 4-oxazolecarboxylic acid esters 379 as p-hydroxy-a-amino acid synthons. They described a straightforward synthesis of 379 by acylation of an isocyanoacetic acid ester with an a-alkoxyacid 378 in the presence of diphenylphosphorylazide (DPPA) or diethylphosphoryl cyanide (DPPC) followed by base-catalyzed cyclization (Scheme 1.104). The reaction conditions do not epimerize optically active a-alkoxyacids. Dilute acid hydrolysis of 379 and reaction with (600)2 affords the protected aminotetronic acids 380. Stereoselective hydrogenation of 380 then yields the 1,4-lactones 381, key intermediates in the synthesis of amino sugars. A variety of a-alkoxyacids were studied, and some examples are shown in Table 1.30. 

---