Acetonide nitrogen

Figure 27. Epoxide hydrolase catalyzed kinetic resolution of c/.v-2-ethyl-3-methyloxirane and formation of 2i ,3f -2,3-pentanediol as monitored by complexation gas chromatography on 0.08 M nickel(II) bis[3-(heptafluorobutanoyl)-(1 / )-camphorate] in methylpolysiloxane [25 m x 0.25 mm (i.d.) glass capillary column. 95CC, 1.1 bar nitrogen]191 2,3-pentanediol as acetonides 0.14 M nickel(ll) bis[3-(heptafluo-robutanoyl)-(l /t,2S)-pinan-4-onatc]151 in SE-30. Note that there is a change in the numbering of the chiral carbon atoms of the oxiranc vs. the diol due to nomenclature requirements.

This operation introduces the nitrogen moiety with the required configuration. Acetonide methanolysis followed hy methanolysis of the benzoates and acetylation generates pyranoside... 

Three of the five fragments have now been assembled, and only the two amine alkylations remain. The first alkylation makes use of the epoxide to introduce the required 1,2-amino-alcohol functionality. The protected enantiomerically pure piperazine reacted with the epoxide, and the product was treated with acid to deprotect both the second piperazine nitrogen and the acetonide group left over from the earlier chiral auxiliary step. The newly liberated secondary amine was alkylated with the reactive electrophile 3-chloromethyl pyridine, and the final product was crystallized as its sulfate salt... 

A thermal gravimetric analysis performed on triamcinolone acetonide (Squibb House Standard 45885-008) 2 showed a 1.0% weight loss complete at about 105°. The measurement was performed under nitrogen sweep the heating rate was 15°/min. Additional weight was rapidly lost after the sample had melted at 300°. 

In the following case, it was anticipated that the nitrogen would participate in the iodocyclization but instead the acetonide proved more reactive. ... 

Sample preparation 1 mL Plasma + 4 mL 59.5 ng/mL triamcinolone acetonide in dich-loromethane, shake at high speed for 15 min, centrifuge at 2000 rpm for 10 min, remove aqueous layer, add 5 mL saturated sodium bicarbonate solution to the organic layer, shake at high speed for 5 min, centrifuge at 2000 rpm for 10 min, remove aqueous layer. Place organic layer in a pointed tube and evaporate to dryness at 45° under a stream of nitrogen. Reconstitute with 50 p.L mobile phase, inject 20 xL aliquot. 

But the Merck chemists noticed that amino alcohol itself, certainly once protected, has a remarkable similarity to Evans oxazolidinone auxiliaries anyway, and it turns out that this amino alcohol will function very successfully as a chiral auxiliary, which does not need to be removed, avoiding waste and saving steps The amino alcohol was acylated with the acyl chloride, and the amide was protected as the nitrogen analogue of an acetonide by treating with 2-methoxypropene (the methyl enol ether of acetone) and an acid catalyst. The enolate... 

Ring opening of the penicillanic nucleus at the bond connecting C3 with the P-lactam nitrogen occurs on the carbinol 170, which indeed exists as an equilibrium mixture of cyclic hemiaminal and acyclic 1/f-azetidinone-aldehyde 171 [105]. Sodium borohydride reduction delivered the corresponding carbinol, easily convertible (2,2-dimethoxypropane, BF3-Et20) to the acetonide 95c [106]. As previously mentioned, the latter is a convenient substrate for the introduction of Cg substituents. 

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