Acetals reductive opening, selective protection

The pyrrolidine derivative 314, a skeletal analog of the antitumor antibiotic anisomycin, was synthesized from the acetal derivative 16b. The 5-OH group of 16b was tosylated and then substituted with sodium azide. Reduction (sodium borohydride) of the lactone group afforded an open-chain derivative, which was selectively protected to give 313. Hydrogenation of the azide function, followed by p-toluenesulfonylation, led to 314 by an intramolecular nucleophilic displacement (284). 

OH free Here, for all the three monosaccharides, a derivative with the 4-OH free can be obtained from the 4,6-O-benzylidene derivative through regioselective reductive opening. Formation of the 4,6-acetal with consecutive 2,3-protection (acetylation, benzoylation, benzylation) and reductive opening using various reagents yields the desired compounds. In mannosides, the selective formation of the 4,6-6>-acetal is not trivial, but can be accomplished with a 50 to 70% yield. 

Besides being useful for selective protection of monosaccharides, cyclic acetals can display a number of interesting reactions, such as reductive or oxidative ring opening, that amplify the synthetic interest of these protecting groups [125]. 

Alkenes are converted to epoxides by oxidation with peroxy acids, and thereby they are protected with regard to certain chemical transformations. Alkaline hydrogen peroxide selectively attacks enone double bonds in the presence of other alkenes. The epoxides can be transformed back to alkenes by reduction-dehydration sequences or using triphenylphosphine, chromous salts, zinc, or sodium iodide and acetic acid. A more advantageous and fairly general method consists, however, of the treatment of epoxides with dimethyl diazomalonate in the presence of catalytic amounts of binuclear rhodium(II) car-boxylate salts. This deoxygenation proceeds under neutral conditions and without isomerization or cy-clopropanation of the liberated alkene (Scheme 97). Furthermore, epoxides can be converted to alkenes with the aid of various metal carbonyl complexes. Thus, they may be nucleophilically opened with... 

The synthesis of 188 from epoxide 189 was done as shown in Scheme 25. Epoxide opening with a propargyl alane reagent [124], protection-deprotection of the alcohol functions, and Redal reduction led to the -allylic alcohol 194, also obtained by another route [116]. Asymmetric epoxidation-Redal epoxide opening [60-62] followed by silylation and debenzylation led to intermediate triol 195. Selective six-membered acetal formation and primary alcohol oxidation then furnished building block 188. 

The former synthesis proceeds via epoxide 278 which was ring opened by azide, the resulting alcohol was protected and full reduction of the lactone and mesylation gave 279. Reductive cyclization and deprotection then provided 280 (Scheme 23). The 6-epi analogue 111 was prepared by converting 275 to pyrrolidine 276. Selective acetal removal and primary hydroxyl mesylation then allowed reductive cyclization followed by deprotection to give 277. Similar chemistry was also used to convert 281, closely related to 275, to (2R)-2-hydroxy-6-e/ /-castanospermine 282. ... 

---