| Summary: | 博士 === 國立清華大學 === 化學系 === 93 === Part I: Applications in asymmetric alkylation, asymmetric aldol reaction and asymmetric imine-aldol reaction of a novel chiral 1,3-oxathiolan-5-one 28, derived from chiral auxiliary N,N-diisopropyl-10-camphor sulfonamide 22 through dimethoxy ketal 25, are studied.
In the asymmetric alkylation reactions using 1,3-oxathiolan-5-one 28 furnished the alkylation product 29 as a single isomer. Removal of the auxiliary from compound 29d via methanolysis under acidic conditions provided methyl 3-phenyl2-sulfanyl propanoate (R)-56a in 100% optical purity. Similarly when 1,3-oxatiolan-5-one derivatives 29a and 29d were subjected to further alkylation gave compounds 55 as the only products. Basic methanolysis of the compounds 55d and 55e gave methyl-2-methyl-3-phenyl-2-sulfanyl propanoate: (R)-56b, (S)-56b in 100% optical purity.
1,3-oxathiolan-5-one 28 with aldehydes in asymmetric aldol reaction gave moderate selectivities. In the cases of aromatic or conjugated aldehydes, when an additive LiCl was added, anti products 71 were formed in major; while addition of HMPA saw the increase in syn products 72. In contrast, isobutyraldehyde and propionaldehyde offered single isomers.
Asymmetric aldol reaction was extended to asymmetric imine-aldol reaction. Initially, N-tosylaldimines 75 were prepared from aldehydes and p-toluenesulfanamide under the catalytic influence of PPTS in benzene. Moderate selectivities were obtained similar to the asymmetric aldol reactions, on treating N-tosylaldimines with 1,3-oxathiolan-5-one 28. Additives provided an increase in either syn-products 89 (LiCl) or anti-products 90 (HMPA).
Part II: Application of asymmetric imine-aldol reaction in the synthesis of antibiotic deoxyaminosugar – daunosamine and staurosporine is studied. Initiating our strategy from racemic starting material, thioglycolic acid with camphor sulfonamide 22 as chiral auxiliary provided daunosamine in 6 steps (namely asymmetric aldol reaction with compound 28 to induce chirality at C3 position, asymmetric cis-dihydroxylation to create C4 and C5 chiral centers followed by reduction, acid catalyzed isomerization and deprotection) and 20% overall yield. Compound α-D-118 from the intermediary step in the synthesis of daunosamine was used in the preparation of compound 177, an acyclic form of amino sugar, a potential intermediate for the efficient synthesis of staurosporine. The synthesis of compound 177 could be accomplished in 4 steps from compound α-D-118 which can be cyclized to get amino sugar part of staurosporine and further complete the total synthesis.
|
|---|
