Acetonide group

Unique chemistry is associated with the cyclopentenone all five carbon atoms can be functionalized, and the endo-methyl groups of the acetonide assure clean stereoselective addition of the alkenylcopper reagent from the convex side. The use of the acetonide group to control enolate regioselectivity and to mask alcohols should be generally applicable. 

Treatment of cyclic vinylaziridine 105 with organocuprates of the R2CuLi type proceeds in a highly syn-selective manner (Scheme 2.29) [46], The syn stereochemistry of the reaction reflects the effect of the acetonide group, which directs the nucleophilic attack to the less hindered a-face. The formation of SN2 products 109 from the cyclic (chlorovinyl)aziridine 107 can be explained by assuming a syn-SN2 ... 

To avoid the retro-Diels-Alder reaction, 56 was dihydroxylated prior to the introduction of the bromine atom (57). Removal of the acetonide group followed by cleavage of the diol afforded a bis-hemiacetal. Selective reduction of the less-hindered hemiacetal group gave 58. The remaining hemiacetal was protected, and the ketone was converted to an enol triflate, thus concluding the synthesis of the electrophilic coupling component 51. 

Metabolism was studied with halcinonide labelled with carbon-14 in the 2-position of the acetonide group. It was administered intravenously to dogs at a dose of 5 mg/kg. The major portion of the radioactivity was excreted in bile. Radio-autography of bile showed at least 10 distinct metabolites to be present. Four of the metabolites were identified. The two most abundant metabolites, that were identified, accounted for 43% (Figure 8, Ml) and 30%(M2) of the radioactivity. The two minor metabolites (M3 and M4) accounted for 2% each. In dog urine, these four metabolites (Ml-4) accounted for 10, 15, 5 and 18% of the radioactivity, respectively. In dog blood, unchanged halcinonide and metabolites M3 and M4 each accounted for about 15% of the radioactivity. Ml and M2 were not detected. 

Intramolecular aminomercuration.1 The key step in a synthesis of ( —)-deoxoprosophylline (4), a piperidine alkaloid, from (S)-serine (1) is aminomercuration of 2. This step proceeds stereoselectively to give 3 with only traces of the C8-epimer. Hydrolysis of the acetonide group furnishes 4. 

In the case of xanthates, no photoreduction is observed but a more complex deprotection of acetonide groups at C-5, C-6 is obtained with subsequent formation of or/Aotrithiocarbonates in the presence of air [89]. 

In contrast, epoxidation with Payne s reagent results only in 4. The epoxide 3 has been used to prepare methyl 6a-fluoroshikimate (5) by treatment with HF in pyridine and removal of the acetonide group. 

Treatment of 2-chloroglycidic esters 621 with magnesium chloride in THF under reflux forms the intermediate 3-chloro-2-keto ester 622. Cyclization occurs upon deprotection of the acetonide group, followed by elimination of water and tautomerization to afford 4-chloro-3-hydroxy-2//-pyran-2-ones in good yield (Scheme 135) <2004TL6299, 2005T2541>. 

Macrolactonizathn with inversion. Lactonization of the optically active seco-acid 1 with P(C sH,), and DEAD followed by hydrolysis of the acetonide group gives the cyclic dilactonc colletodiol (2), formed with inversion of configuration at the hydroxyl-bearing carbon. Lactonization of 1 with 2,4,6-trichlorobenzoyl chloride and tdethylamine (9, 478-479) furnishes 6-epicolletodiol after deprotection. 

Spiroketalization, The synthesis of talaromycin B (3) with four chiral centers by cyclization of an acyclic precursor presents stereochemical problems. A solution involves cyclization of a protected (3-hydroxy ketone with only one chiral center.1 Because of thermodynamic considerations (i.e., all substituents being equatorial and the anomeric effect), cyclization of 1 with HgCl2 in CH3CN followed by acetonation results in the desired product (2, 65% yield) with a stereoselectivity of —10 1. Final steps involve conversion of the hydroxymethyl group to ethyl by tosylation and displacement with lithium dimethylcuprate (80% yield) and hydrolysis of the acetonide group. 

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... 

Removal of the isopropylidene (acetonide) group. Hampton et al. found that for a given concentration of acid (0.01 N), the conversion of isopropylideneuridine (1) into uridine (2) proceeds ten times more rapidly in ethyleneglycol solution than in water. Methanol and ethanol were significantly less effective. 

More recently, Lewbart3 reported selective hydrolysis of the acetonide group of 17,20 -isopropylidenedioxy-5/3-pregnane-3a,21-diol diacetate (5) with retention of the primary and secondary acetoxy groups. 

A facial synthesis of tetrazole 62 as an intermediate for the synthesis of 1-deoxymannojirimycin (2) has been reported (Scheme 11). The azide 54, obtained from L-gulonolactone 53, " was treated with ammonia in methanol to produce 59, which was reacted with trifluoroacetic anhydride in pyridine to give the nitrile 60. When the azidonitrile 60 was heated in toluene for 3 days, an efficient 1,3-dipolar cycloaddition took place, resulting in the formation of the tetrazole 61. Removal of both the silyl and acetonide groups in... 

Alternatively, the readily accessible 1,2-0-isopropylidene-a-D-xylofuranose (41) was used for the total syntheses of the natural (-l-)-sesbanimide A (1) and the unnatural (-)-sesbanimide B (3) (Scheme Benzylation of 41 afforded 42 whose acetonide group... 

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