2-Trimethylsilyl-1,3-propanediol

Chiral 2-alky 1-1,3-propanediols.i Reaction of ( —)-menthone (1) with the bis(trimethylsilyl)ether 2 catalyzed by trimethylsilyl triflate gives the more stable equatorial isomer (3) of a spiroketal. Ring cleavage of the equatorial bond of the... 

S)-l-Alkyl-l,2, 4-tetrahydroisoquinolines. The bis(trimethylsilyl) ether (2) of 1 has been used as a chiral auxiliary to effect alkylation of tetrahydroisoquinoline (equation 1) with high enantioselectivity. The chiral propanediol is much more effective than (R)-(— )-a-phenethylamine, and moreover leads consistently to (S)-l-alkyl derivatives. 

Optically active 2-substituted- 1,3-propanediol derivatives were prepared as shown in equation 45. The bis-trimethylsilylated 1,3-diols were condensed with /-menthone in the presence of trimethylsilyl triflate to give the corresponding diastereomeric ketals, which were separated and subjected to further transformations. For example, the cleavage was carried out via a Mukaiyama reaction to generate the a-alkoxy ketone, which could be protected and then cleaved to the optically active, unsymmetrical, monoprotected 1,3-diol52. 

The branched-chain tetritol, 2-C-(hydroxymethyl)glycerol, was synthesized by diazotization of 2-amino-2-(hydroxymethyl)-1,3-propanediol [tris(hydroxymethyl)aminomethane Tris]. The total crude product that resulted from this synthesis gave, after per(trimethylsilyl)ation, the three peaks shown in Fig. 17. 2-C-(Hydroxymethyl)glycerol from the per(tri-methylsilyl)ated Tris corresponded identically in retention time to the peak for the compound in the tetritol region of formose, and a comparison of the mass spectra of these two species (see Fig. 17) showed that they are identical. 

The EtOAc-soluble fraction of the alkaline hydrolysate of 37 containing a mixture of fatty acid units was treated with ozone followed by NaBH4 reduction. Trimethylsilyl (TMS) derivatives of the ozonolysis product were subjected to chiral CjC analysis (Chirasil-Val) to give a p identical with the TMS-derivative of (i0-l 2-propanediol. Consequently, the absolute configuration of C-9 " position of 37 was assigned as S. 

Hydroboration of Silylalkenes and SUylalkynes. (Z)-l-Trimethylsily 1-1-alkenes react with DBBS to produce ge/rniime-talloalkanes, which upon oxidation afford alcohols containing the trimethylsilyl group in high yields (72-84%) (eq 13). Unexpectedly, desilylation of (2)-2-(l-trimethylsilyl-l-hexenyl)dibromo-borane is observed during the hydrolysis followed by treatment with 1,3-propanediol. 

Identification of N-acetyl-g-(p-tolyloxy)alanine in the urine of rats treated with 3-(p-tolyloxy)-l,2-propanediol. The Mephenesin analogue, 3-( -tolyloxy)-l,2-propanediol was administered to rats and urinary metabolites were identified by GC-MS. In the alkaline extracts, the unchanged substance was the major component. Fig. 1 (top) shows the gas chromatographic patterns of acidic extracts from the urine of rat treated with 3-( -tolyloxy)-1,2-propanediol. For derivatization, hexamethyldisilazane was used as the trimethylsilylating agent. The column temperature was programmed from 200 C at 3 C/min. The large peak pointed by a small arrow was identified as B-( -tolyloxy)-lactic acid. 

FIG. 2. The mass spectrum of the unknown metabolite from 3 ( tolyloxy)--1,2-propanediol-treated rats. Trimethylsilylation was done with hexamethyldisilazane. 

Identification of N-acetyl-3" phenoxyalanine in the urine of rats treated with 3-phenoxy-l,2-propanediol. The other Mephenesin analogue, 3-phenoxy-l, 2-propanediol was given to rats and the urine sample was analyzed by GC-MS. In the alkaline extracts, the main component was 3-phenoxy-l, 2-propanediol. The gas chromatogram of the acidic extracts was obtained after trimethylsilylation (shown in Fig. 1, bottom). A major metabolite was 3 phenoxylactic acid corresponding to the large peak indicated by the small arrow. 

By gas chromatography-mass spectrometry N-acetyl-p-aryloxy-alanine was identified as a metabolic product of 3-aryloxy-1,2-propanediol in rats. Although we have not yet obtained authentic N-acetyl-g-(2 -tolyloxy) alanine and N-acetyl-g-phenoxyalanine, the proposed structure was supported by following data 1. The gas chromatographic properties such as heat instability and retention time were very similar to that of N-acetyl-6-(o -tolyloxy)alanine TMS ester. 2. The mass spectra of mono-trimethylsilylated N-acetyl-3 ( 7tolyloxy)alanine and N-acetyl-3 phenoxyalanine closely resembled that of N-acetyl-g-(o-tolyloxy)alanine, the structure of which was confirmed by high resolution mass measurement, acid hydrolysis and TLC, 3. These two metabolites showed very similar properties to N-acetylphenyl alanine on trimethyls ilyl at ion and similar mass spectral fragmentations. 

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