A-acetoxyamide

The importance of proper immobilization of enzymes can be shown in the kinetic resolution of racemic a-acetoxyamides. This group of compounds is an important class of chemicals since they can be readily transformed into a-amino acids [17], N-methylated amino acids, and tripeptide mimetics [18], amino alcohols [19], 1,2-diols [20], 1,2-diamines [21], and enantiopure l,4-dihydro-4-phenyl isoquinolinones [22]. 

For the kinetic resolution of racemic a-acetoxyamide 6 several native enzymes were used (Scheme 5.5). The native Upases from Pseudomonas cepacia (PCL) and porcine pancreas (PPL) showed the highesL although stiU unsatisfactory, enantios-electivity ( = 5.1 and 3.5, respectively). Upon immobilization into a solgel matrix, the enantioselectivity of PCL was improved significantly to 30.5. The covalent immobilization on Eupergit increased the enantioselectivity even more (34.0) [23]. 

Recently, an interesting example of the enzymatic kinetic resolution of a-acetoxyamide 8 was demonstrated using native wheat germ lipase and immobilized lipase PS (AMANO) (Scheme 5.6). 

The dissolving aluminium, lead bromide system has been combined with a Lewis acid in tetrahydrofuran to effect the combination of an allyl bromide with an acetal or an a-acetoxyamide, Altuninium chloride is employed as the Lewis acid to... 

Spirocyclic triazolines are rare entities, however reduction of a-azidocycloalkyl-nitriles (or amides) affords spirocyclic triazolines in variable amounts. Azide (85a) afforded cyanoamine (86a) and spiro-l,2,3-triazole (87) in 56% and 16% yield, respectively. Similarly, azide (85b) afforded the spiro-l,2,3-triazolone (88) in 25% yield along with some starting material, some reduced linear triazine and the amine (86b). When 88 was thermolyzed in acetic acid, the a-acetoxyamide (89) was obtained [94JOC(59)6853]. 

Synthetic routes to this class of compounds have often been long and complicated the original route for AG5473/5507 required 20 steps. Therefore, the ability to reduce the number of steps has considerable advantage. Guo and colleagues have developed an 11-step synthetic route to AG5473/5507.35 This sequence incorporates an effective ozonolysis protocol for the introduction of an aldehyde moiety 23 that is an essential step to the production of the tricyclic diazamide core 24 (Scheme 11.6). In the reaction sequence, a protected acetylene is added to acetoxyamide 25, to... 

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