(3S,4S)-3-氨基-4-氨羰氧甲基-2-吖叮啶酮-1-磺酸钠衍生物的合成与抗菌活性

Synthesis and Antibacterial Activity of Sodium (3S, 4S)-3-Amino-4-[(carbamoyloxy) methyl]-2-oxoazetidinone-1-sulfonate Derivatives

以(3S,4S)-3-氨基-4-氨羰氧甲基-2-吖叮啶酮-1-磺酸钠为母核,选择D-(-)-2-(7或8-甲氧基香豆素-3-甲酰胺基)-2-苯或4-羟基苯乙酸和D-(-)-α-(4-乙基-2,3-二氧-1-哌嗪甲酰胺基)-2-苯或4-羟基苯乙酸作为边链,合成6个新的单胺菌素衍生物:(3S,4S)-3-[D-(-)-2-(8或7-甲氧基香豆素-3-甲酰胺基)-2-(苯或4-羟基苯)乙酰胺基]-4-氨羰氧甲基-2-吖叮啶酮-1-磺酸钠Ⅳ_(1-4);(3S,4S)-3-[D-(-)-α-(4-乙基-2,3-二氧-1-哌嗪甲酰胺基)-2-(苯或4-羟基苯)乙酰胺基]-4-氨羰氧甲基-2-吖叮啶酮-1-磺酸钠Ⅳ_(5-6)。初步体外抑菌试验表明,化合物Ⅳ_5,Ⅳ_6对革兰氏阴性菌有较强的抗菌活性。

Sodium (3S, 4S)-3-amino-4-[(carbamoyloxy) methyl]-2-oxoazetidinone-1-sulfonate was utilized as a monocyelic nucleus. D-(-)-2-(8(7)-methoxycoumarin-3-carboxamido)-2-(phenyl or 4-hydroxyphenyl) acetic acid and D-(-)-α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-2-(phenyl or 4-hydroxyphenyl) acetic acid were being used as the side-chain acid. The six novel derivatives of monobactam were synthesized: Sodium (3S, 4S)-3-[D-(-)-2-(8(7)-methoxycoumarin-3-carboxamido)-2-phenylacetamido] -4- [(carbamoyloxy) methyl]-2-azezidinone-1-sulfonate Ⅳ_1, Ⅳ_3; Sodium (3S, 4S)-3-[D-(-)-2-(8(7)-methoxycoumarin-3-carboxamido)-2-(4-hydroxy) phenylacetamido]-4-[(carbamoyloxy) methyl]-2-azetidinone-1-sulfonate Ⅳ_2, Ⅳ_4; Sodium (3S, 4S) -3-[D-(-)-α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-2-(phenyl or 4-hydroxyphenyl) acetamido]-4-[(carbamoyloxy) methyl]-2-azctidinone-1-sulfonate Ⅳ_5, Ⅳ_6. Preliminary antibacterial tests of these six derivatives were carried out. Compounds Ⅳ_5, Ⅳ_6 showed obvious antibacterial activity against Gram-negatives.