105(P34) β,γ-不飽和α-ケトエステルを合成ブロックとして用いるsyn-β-アミノ-α-ヒドロキシ酸の立体選択的合成(ポスター発表の部)

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In recent years, there has been considerable interest in β-amino-α-hydroxy acids, the crucial components of some peptide-mimic compounds such as KRI-1314, KRI-1230 and Microginin, which possess renin or angiotensin-converting enzyme inhibitory properties. Herein, we describe enantioselective synthesis of β-amino-α-hydroxy acids starting from (β,γ-unsaturated α-keto esters. The reaction of methyl 2-(trimethylsiloxy)acryrate (2), easily prepared from methyl pyruvate, with acetals 1 or aldehydes gave β,γ-unsaturated α-keto esters 3, which were then transformed into (-)-trans-2-phenylcyclohexyl esters 7a,b. Diastereoserective reduction of the α-carbonyl moiety using L-selectride provided (2R)-β,γ-unsaturated α-hydroxy esters 8a,b. Thus obtained allylic alcohol derivatives 8a,b were converted into the corresponding carbamates, which were cyclized by activation with iodine in the presence of sodium carbonate, providing trans-oxazolidinones 9a,b in a stereoselective manner. The oxazolidinones 9a,b were easily converted into the desired (2R,3S)-3-amino-4-cyclohexyl-2-hydroxybuthylic acid (12a) and (2R,3S)-3-amino-2-hydroxy-5-methylhexanoic acid (12b) by usual deprotecting procedures. Synthesis of (2S, 3R)-3-amino-2-hydroxydecanoic acid (12c) was achieved via (+)-trans-2-phenylcyclohexyl ester 7c in a similar manner as described above.
天然有機化合物討論会の論文
1996-09-02