100(P22) キラルビルディングブロックとしてのオキサゾリジノンエステル : アミノアルコール類の立体選択的合成(ポスター発表の部)

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γ-Hydroxy-β-amino alcohols are of major importance for partial structure of biologically active compounds such as sphingosine, sphingomyeline, and azasugars, and the corresponding amino acids are found as constituents of biologically important peptides. In the relative stereochemistry between the hydroxyl and amino groups of these biologically important compounds, syn stereochemistry is generally found in naturally occurring hydroxyamino acids, whereas that of sphingolipids and azasugars is anti. It is, therefore, very attractive subject to establish the method for stereoselective synthesis of both syn and anti amino alcohols from the common chiral building block. Now, we report the stereocontrolled syntheses of β-hydroxyamino acids, sphingosine which is an inhibitor of protein kinase C, sphingomyeline which is an important source of a lipid second messenger in cell membranes, and azasugars which are potent glycoside inhibitor, from 4-methoxycarbonyloxazolidinone derivative 2 which is easily prepared from glycidol. Reaction of (R)- and (S)-glycidol with benzylisocyanate in the presence of triethyl-amine produced 4-hydroxymethyloxazolidinone derivative in one step. Monoalkylation of the ester 2 derived from the obtained alcohol with various alkyl, alkenyl and alkynyl lithium compounds was successful under -100℃ in THE to yield the corresponding ketones in high yield. Highly syn selective reduction of the alkyl and alkenyl ketones obtained was achieved with L-Selectride^[○!R], whereas anti selective reduction of the alkenyl and alkynyl ketones was successfully achieved by use of bulky alkoxyisobutylaluminum reagent 6. The occurrence of the stereoselectivity is understandable by considering the conformational analysis of the reaction pathway. Utilizing this strategy, we achieved the stereoselective syntheses of all stereoisomers of threoninol, hydroxyphenylalaninol, sphingosine and sphingomyeline analogs. We also established the synthesis of deoxy-mannojirimycin, deoxyaltrojirimycin and deoxygaractostatin through bicyclic oxazolidyl-piperidine derivative 18, which was prepared by the same strategy followed by cyclization. The stereocontrolled introduction of vicinal three hydroxyl groups in deoxyazasugars were realized by osmilation or epoxidation followed by diaxial epoxide ring opening. The compound 18, thus, is a flexible synthetic intermediate of deoxyazasugars. Thus, the ester 2 was proved to be very useful chiral building block equal to the Garners oxazoline chiral building block 1 for the synthesis of various amino alcohols.
天然有機化合物討論会の論文
1998-08-31

100(P22) キラルビルディングブロックとしてのオキサゾリジノンエステル : アミノアルコール類の立体選択的合成(ポスター発表の部)

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