Castanospermine stereoselective

Stereoselective allylation of aldehydes is another preferred strategy for the synthesis of appropriate intermediates for the total synthesis and introduction of hydroxy functionalities. Park and co-workers <2003S2473> proposed a synthesis of castanospermine 228 through a key indium-mediated allylation in the presence of (+)-cinchonine of an a-amino aldehyde 247 derived from D-glucono-O-lactone (Scheme 53). 

Synthesis from xylose The xylose derivative 47, obtained from 5,5-bis-benzyloxy-7-oxa-bicyclo[2.2.1]hept-2-ene (45), has been used in the synthesis of (-P)-castanospermine (1) (Scheme 6). Bromination of 45 occurred exclusively on the less hindered convex face of 45, followed by stereoselective migration of the endo OBn group of the acetal to give 46, which subsequently converted to 47. Mesylation of 47 followed by cyclization with ammoifia gave 48, whose protection, hydrolysis, acetylation and cyclization by an intramolecular Wittig-Homer condensation gave 49. Conversion of 49 into epoxide 50... 

Castanospermine has been synthesized by stereoselective reduction of cyclic sulfate with sodium borohydride as shown in Eq. (50) (96TL547). 

Regio- and stereoselective ring opening of 283 with Et2AlN(CH2Ph)2, prepared in situ from Et2AlH and dibenzylamine, furnishes in 78% yield the amino alcohol 287, which is converted in four steps to aldehyde 288. An aldol reaction of 288 with lithio ethyl acetate proceeds by a nonchelated Felkin-Anh pathway to provide predominantly the a /-selective a-hydroxy ester (89 11 diastereomeric mixture), which is tosylated and separated chromatographically to afford 289. This compound is converted in four steps to (+ )-e/7/-castanospermine (290) (Scheme 67). 

Azides can partake in stereoselective dipolar cycloaddition reactions with olefins. The unstable resulting triazolines typically expel N2 under the conditions of the cycloaddition reaction, leading to the corresponding stable azir-idines. Cha has reported that heating of azide 32 leads directly to aziridine 33 as a single diastereomer (Scheme 18.8) [55]. The allylic stereocenter resident in 32 thus effectively controls the stereochemical outcome of the transformation. The product aziridine 33 was subsequently elaborated into 6,7-di-epi-castanospermine (34). 

Starting from the AT-Cbz-protected aldolase product 6, aza sugar 7 has been obtained stereoselectively by internal reductive amination as an analog of the bicyclic, indolizidine-type glycosidase inhibitor castanospermine [66]. Also, it had been recognized that the C12-C20 sequence of the macrolide antibiotic amphotericin B resembles the P-pyranose tautomer of 3 [76]. Thus, the branched-chain manno-configurated substrate 10 [77] was successfully chain-extended under NeuA catalysis to )deld the potential amphotericin B synthon 11 (Fig. 8) in good yield. 

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