5-Solketal

Application to solketal and other primary and secondary alcohols... 

The low-temperature method has been applied to some primary and secondary alcohols (Fig. 1) For example, solketal, 2,2-dimethyl-1,3-dioxolane-4-methanol (3) had been known to show low enantioselectivity in the lipase-catalyzed resolution (lipase AK, Pseudomonas fluorescens, E = 16 at 23°C, 27 at 0oc) 2ia however, the E value was successfully raised up to 55 by lowering the temperature to —40°C (Table 1). Further lowering the temperature rather decreased the E value and the rate was markedly retarded. Interestingly, the loss of the enantioselectivity below —40°C is not caused by the irreversible structural damage of lipase because the lipase once cooled below —40°C could be reused by allowing it to warm higher than -40°C, showing that the lipase does not lose conformational flexibility at such low temperatures. 

Temperature effect in the lipase-catalyzed kinetic resolution of solketal... 

As described above, the temperature effect is useful for enhancing the enantioselectivity however, one problem is the decrease in the reaction rate. For example, although in a lipase AK-catalyzed resolution of solketal, the E value (9 at 30°C, Table 1, entry 1) is increased up to 55 by lowering the temperature to —40°C, 10 times the amount of lipase and 8-fold the reaction time are required as compared with those at 30°C. Thus, the rate of acceleration is an important subject especially to make the low-temperature reaction practical. 

Fig. 14. Chiral dendrimers 31 (prepared as racemic mixture) with a core chirality center. Compounds 32 and 34 are derived from (S)-solketal 33 as enantiopure precursor [61,64,66]...

Salicylaldehyde, h94 Solketal, d599 Stearamide, o2 Stearic acid, o5 Stearyl bromide, b385... 

Solketal Acrylate. 17 has been reported previously (3) and was synthesized In this case via standard (4) ester exchange (aluminum Isopropoxide catalyzed) from methyl acrylate and the commercially available acetone ketal of glycerine (solketal, Aldrich Chemical Co.). 

Incorporation Into a co- or terpolymer of a d1ol containing monomer such as solketal acrylate (SA, H, a comonomer readily hydrolyzed by aqueous add to a diol) likewise Increases crosslinking (Scheme 4). Such polymers exhibit Improved dry, wet and solvent resistance (Table V). Alternatively, half of the ABDA comonomer can be substituted with SA, without significantly degrading properties vs the Initial ABDA only sample. 

Lipase catalysed hydrolysis of racemic esters of the important chiron solketal , 1, 2-0-isopropyhdene glycerol, are not very stereospecific due to the fact that they are primary esters. Secondary esters usually show much higher -values. Table 2.1 shows -... 

A)-solketal butyrate, and (S)-solketal butyrate ((D)+(L)-solketal, Fluka, prepared according to a known procedure [21])... 

The reverse reaction consisting of the PCL-catalyzed hydrolysis of the esters of three primary alcohols 2-methyl-3-phenyl-1-propanol 4, 2-phenoxy-l-propanol 5 and solketal 6 was studied by Kazlauskas et al.61 An enhancement of the enantioselectivity E was observed when changing the solvent from ethyl ether/phosphate buffer to 30% n-propanol in phosphate buffer and when changing the substrate from 1-acetate to 1-heptanoate. The same enhancement in E value was observed with 5 but there was no significant increase towards the alcohol 9. 

In the first step sodium hydride was used as a base in THF to introduce a benzyl protective group to the sn-3 position of the glycerol moiety by a Williamson ether synthesis using benzyl bromide. The benzylated solketal adduct was not isolated but introduced to deprotection of the isopropylidene... 

Finally, all corresponding optical antipodes of enantiopure TAG of the MLM type described above have also been successfully synthesized using optically pure solketal of opposite configuration (R) as a chiral precursor. Otherwise the methodology was identical and very similar results were obtained with reverse signs of the specific rotation values as was anticipated. 

Many organic solvents are used in pharmaceutical products. These include propylene glycol, polyethylene glycols, ethanol, dimethyl sulfoxide, N-methyl-2-pyrrolidone, glycofurol, Solketal, glycerol formal, and acetone evidence of harm from such solvents is scant (2). 

Sakai T, Kishimoto T, Tanaka Y, Ema T, Utaka M (1998) Low-temperature method for enhancement of enantioselectivity in the lipase-catalyzed kinetic resolutions of solketal and some chiral alcohols. Tetrahedron Lett 39 7881-7884... 

A very different situation was observed when the resolution of racemic 1,2-0-isopropyhdeneglycerol (IPG or solketal) was studied [19]. In this case, the kinetics of the esterification with butyric acid catalyzed by A. oryzae MIM and R. oryzae CBS 112.07 were investigated by carrying out independent batch tests on the commercially available R- and S-IPG (Table 6.4). 

DIOXOLANE 2,2-DIMETHYL-4-OXYMETHYL-U-DIOXOELNE DIOXOLANE pOT) GIE GLYCEROLACETONE GLYCEROL DIMETHYL-KETAL 4-HYDROXYMETH X-2,2-DIMETHYL-l,3-DIOXOLANE ISOPROPYLIDENE GLYCEROL l,2-o-ISOPROPYLIDENE GLYCEROL SOLKETAL... 

The most efficient method for the synthesis of racemic plasmenylcholines (52), an important class of glycerophospholipids, requires only six steps beginning from the inexpensive starting materials solketal or glycerol and acrolein. This method may also be applicable to the synthesis of chiral plasmenylcholines (Figure 13). ... 

R)-Solketal by eiiantioselective oxidation of racemic solketal Oxidase... 

S-Solketal (15) can be obtained by the oxidative cleavage of o-mannitol (16) (Scheme 9). Of course, the use of heavy metals in the cleavage reaction does bring along environmental problems. The aldehyde 17, although used for a wide variety of transformations, does suffer from epimerization problems however, additions to the carbonyl group can be manipulated through the use of chelation control [1]. 

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