(3S,4S)-DHGA

合成路线:Treatment of trityl-protected ribofuranoside derivative (I) with SOCl2 and Et3N affords intermediate (II),which is then subjected to a nucleophilic substitution with NaN3 in HMPA and to tosylation with p-TsCl in pyridine to provide (III).Trityl removal of (III) by treatment with H2SO4 in dioxane followed by Sharpless oxidation of the free hydroxyl group with RuCl3 and NaIO4,yields uronic acid derivative (IV),which is then protected with benzyl alcohol,DCC and catalytic DMAP in CH2Cl2 to yield benzyl ester (V).Hydrolysis of (V) with aqueous TFA affords furanose (VI),which is silylated by means of TBS-Cl and imidazole in DMF to provide (VII).Reduction of the azide moiety of (VII) by treatment with 1,3-propanedithiol and Et3N in MeOH,followed by cyclization with Et3N,in DMF gives (VIII).Alternatively,aziridine (VIII) can be obtained by heating (VII) in pyridine in the presence of PPh3,H2O and Et3N.Treatment of (VIII) with Cbz-Cl in CH2Cl2 and aqueous NaOH yields a mixture of alpha- and beta-anomers (IX),which is desilylated without separation step by using tetrabutyl ammonium fluoride (TBAF) in THF in the presence of HOAc to provide beta-hydroxy anomer (X).Oxidation of (X) by means of tetrapropylammonium perruthenate (TPAP) and N-methylmorpholine N-oxide (NMO) in acetonitrile allows obtaining aziridino-gamma-lactone (XI),which then reacts with benzyl alcohol and BF3稥t2O in CHCl3 to give amino acid (XIII) and its lactonized derivative (XII).Both products are finally deprotected by hydrogenolysis over Pd/C in MeOH and the resulting products are separated by a basic anion exchange column (AG1-X4).

参考文献标题:Application of 2,3-aziridino-gamma-lactone methodology toward the enantiospecific synthesis of the (3S,4S) isomer of dihydroxy-L-glutamic acid
文献作者:Dauban,P.; et al.
参考来源:Tetrahedron 1999,55(24),7589


合成路线:Treatment of trityl-protected ribofuranoside derivative (I) with SOCl2 and Et3N affords intermediate (II),which is then subjected to a nucleophilic substitution with NaN3 in HMPA and to tosylation with p-TsCl in pyridine to provide (III).Trityl removal of (III) by treatment with H2SO4 in dioxane followed by Sharpless oxidation of the free hydroxyl group with RuCl3 and NaIO4,yields uronic acid derivative (IV),which is then protected with benzyl alcohol,DCC and catalytic DMAP in CH2Cl2 to yield benzyl ester (V).Hydrolysis of (V) with aqueous TFA affords furanose (VI),which is silylated by means of TBS-Cl and imidazole in DMF to provide (VII).Reduction of the azide moiety of (VII) by treatment with 1,3-propanedithiol and Et3N in MeOH,followed by cyclization with Et3N,in DMF gives (VIII).Alternatively,aziridine (VIII) can be obtained by heating (VII) in pyridine in the presence of PPh3,H2O and Et3N.Treatment of (VIII) with Cbz-Cl in CH2Cl2 and aqueous NaOH yields a mixture of alpha- and beta-anomers (IX),which is desilylated without separation step by using tetrabutyl ammonium fluoride (TBAF) in THF in the presence of HOAc to provide beta-hydroxy anomer (X).Oxidation of (X) by means of tetrapropylammonium perruthenate (TPAP) and N-methylmorpholine N-oxide (NMO) in acetonitrile allows obtaining aziridino-gamma-lactone (XI),which then reacts with benzyl alcohol and BF3稥t2O in CHCl3 to give amino acid (XIII) and its lactonized derivative (XII).Both products are finally deprotected by hydrogenolysis over Pd/C in MeOH and the resulting products are separated by a basic anion exchange column (AG1-X4).
参考文献标题:Synthesis of optically pure 3,4-disubstituted L-glutamates from a novel 2,3-arizidino-gamma-lactone 4-carboxylate derivative
文献作者:Dauba,P.; et al.
参考来源:J Org Chem 1996,61(7),2488