Epoxides, amino functionalization

Numerous carbacyclic, or sulfur-containing, analogues of mono- and difluoronucleo-sides have been synthesized as potential antivirals. In the carbacyclic series, the starting compound is hydroxymethylcyclopentene oxide. Rearrangement of this oxirane creates a new unsaturation that can be oxidized further into another epoxide. An amino function can then be introduced on the 4 position and can be used to build the base (Figure 6.13). 

POMs can he immobilized onto anion-exchange resins and surface-modified metal oxides with quaternary ammonium cation- or amino-functional groups via anion-exchange. Jacobs and coworkers tethered Venturello s catalyst [P04(W0(02)2)4]3-on a commercially available nitrate-form resin with alkylammonium cations and have carried out the epoxidation of allylic alcohols and terpenes with this supported catalyst [166, 167]. The regio- and diastereoselectivity of the parent homogeneous catalysts were preserved in the supported catalyst. For bulky alkenes, the reactivity of the POM catalyst was superior to that of Ti- 3 zeolite with a large pore size. The catalytic activity of the recycled catalyst was maintained completely after several cycles. 

Scheme 17.8 highlights the most recent patented route [via intermediate (1) in the above list] epoxidation of the double bond of 3-(2-chlorophenyl)-2-(4-fluorophenyl)acrylaldehyde is conducted with hydrogen peroxide under basic conditions followed by the reduction of the aldehyde to the corresponding alcohol. The free hydroxyl group is activated by mesylation to the mesyl derivative, which in turn undergoes nucleophilic substitution with symmetrical N-aminotriazole. The attacking nitrogens are the ones free from the N-amino functionality. The N-aminotriazolium obtained is then reduced with sodium nitrite under acidic conditions to afford epoxiconazole. 

The same epoxide 83 can be opened by the amino function of protected amino acids 88 with retention of configuration at this center leading to the Amadori product precursor 89, which, in turn, after oxidation and deprotection, can be converted into the desired Amadori compounds, such as 73 (Scheme 27) [91 ]. 

The approach developed by Danishefsky and co-workers for the construction of sugar derivatives (see Vol.l6,p.126), which employs the initial synthesis of a dihydropyrone derivative by a Lewis acid-catalyzed hetero-Diels-Alder reaction, has been extended to the synthesis of the glycoside derivative (36), x>f DL-llncosamine (Scheme 10). Introduction of the amino-function at C-6 required a circuitous approach Involving 6,7-bromohydrin, 6,7-epoxide, and N-substituted 6,7-aziridine intermediates. ... 

When a better leaving group than LiNSC R (e.g., OMe) is present at the a-position, retention of the potentially useful sulfonamide moiety occurs (e. g., in the conversion of aziridine 271 into the highly functionalized amino ether 272 Scheme 5.69) [98]. It should be noted that the analogous chemistry with epoxides of allylic diethers failed this could again (see above) be possibly due to the higher pKa of the epoxide proton relative to the aziridine proton. 

With a-chloro ketones, lithiated (2S)-2,5-dihydro-2-isopropyl-3,6-dimethoxypyrazincs react at the carbonyl group to give the aldol adducts which, upon subsequent treatment with sodium hydroxide, give the epoxides 413. Hydrolysis leads to fi.y-epoxy amino acids, or further functionalized amino acids when the epoxide is opened with nucleophiles13. 

---