Epoxy sugars

Nucleophilic ring opening of epoxy sugars is a valuable method for the synthesis of many modified sugar derivatives. The reaction is accompanied by Walden inversion, and a wide range of nucleophiles can be used. The cyclic nature of epoxides renders the competing elimination process stereoelectronically unfavourable. For asymmetric epoxides, in principle, two regio-isomeric products can be formed however, in 

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Numerous epoxy sugars have been hydrolyzed in aqueous base, among them almost all the possible 2,3-anhydro-4,6-C>-bentylimethyl glycosides of n-talose,887- 11 u-gulose,697-1611 n-mannose,874 and D-aUose8 - iiM,i4M,i 7t indicated in Eq. (542). 

Several epoxy sugars containing a suitably disposed free hydroxyl group have been shown to yield new anhydro sugars on treatment with aqueous bam or acid. When the free hydroxyl group ict on a carbon atom... 

Epoxy sugars are frequently used as starting compounds in the synthesis of sugar derivatives (compare Section IV) such as halo, amino, azido, thio, deoxy, and branched-chain derivatives. The oxirane ring is in general more reactive than the oxetane or oxolane ring. It is opened with nucleophiles under base or acid catalysis. On the other hand, the oxirane ring remains unattacked under the conditions of catalytic debenzylation on palladium,... 

N. Vethaviyasar, R. Kimmich, and W. Voelter, Specific SN2 substitution in tosyl epoxy sugars, Chem.-Ztg., 101 (1977) 36-37. 

Ogawa later published the synthesis of a 3-amino-3,4-dideoxyhexiu-onic acid in route to ezomycin [24]. In that account, a 1,6-anhydro epoxy sugar was reacted with sodium azide followed by antimony pentachloride to give methyl 3-azido-2-0-benzoyl-a-D-glucospyranoside. Oxidation of the primary alcohol was achieved with potassium permanganate, and reduction of the azide was accomplished with hydrogenation (Fig. 8). 

The starting materials are prepared by oxidation of selectively blocked epoxy sugars with Ru02-NaI04 (3, 243). 

The above described strategy was also tested with the isomeric epoxy sugar 12. Treatment of 12 with the dianion of ferf-butyl acetoacetate affords the regioisomers 16 and 17 in a ratio of 9 1 (75% combined yield). Subsequent mesylation followed by reaction with hydrazine yields the regioi-someric pyradazine derivatives 70 and 71, respectively (Scheme 16). 

Super-hydride (LlBEt H) has been shown to be more effective than other reagents (e.g.. LAH) for reductive cleavage of epoxides and sulphonate esters. Thus methyl a-abequioslde (3) was obtained in 94 yield on reduction of the epoxy-sugar sulphonate (4), while... 

Other examples were also described by Schobert et al ot,P-Unsaturated esters can be prepared in a one-pot process from a variety of alcohols. In the first step, the alcohols are oxidized selectively by PhI(OAc)2/2,2,6,6-tetramethyl-l-piperidinyloxy (TEMPO) to aldehydes that are then subjected to Wittig olefination with ethox-ycarbonylmethylene- or a P-oxomethylenephosphorane (Scheme 94). Substituent Y may include unsaturated, hydroxyalkyl and aryl groups, as well as epoxy-, sugar and pinane-based substituents. 

The action of ammonia or amines on the epoxy sugars results in ring opening with the formation of aminodeoxy sugars or their derivatives. An interesting example is found in the conversion of D-xylose to 3-amino-3-deoxy-D-ribose, a structural component of the antibiotic puromycin (80). The transformation (see formulas on p. 392) is remarkable in that derivatives of all four D-aldopentoses are involved. 

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