申请人:——
公开号:US20020006642A1
公开(公告)日:2002-01-17
The invention relates to a method for preparing a &bgr;-lactam antibiotic, wherein an N-substituted &bgr;-lactam, having general formula (I), wherein R
0
is hydrogen or C
1-3
alkoxy; Y is CH
2
, oxygen, sulfur, or an oxidized form of sulfur; Z is (a), (b), (c) or (d), wherein R
1
is hydrogen, hydroxy, halogen, C
1-3
alkoxy, optionally substituted, optionally containing one or more heteroatoms, saturated or unsaturated, branched or straight C
1-5
alkyl, preferably methyl, optionally substituted, optionally containing one or more heteroatoms C
5-8
cycloalkyl, optionally substituted aryl or heteroaryl, or optionally substituted benzyl; and X is (CH
2
)
m
-A-(CH
2
)
n
, wherein m and n are the same or different and are chosen from the group of integers 0, 1, 2, 3 or 4 and A is CH═CH, C═C, CHB, C═O, optionally substituted nitrogen, oxygen, sulfur or an optionally oxidized form of sulfur, and B is hydrogen, halogen, hydroxy, C
1-3
alkoxy, or optionally substituted methyl, or a salt thereof, is contacted with at least one dicarboxylate acylase, or a functional equivalent thereof, and reacted with a precursor for a side chain of the &bgr;-lactam antibiotic in the presence of at least one penicillin acylase, or a functional equivalent thereof.
本发明涉及一种制备&bgr;-内酰胺类抗生素的方法,其中 N-取代的&bgr;-内酰胺具有通式(I),其中 R
0
是氢或 C
1-3
烷氧基;Y 是 CH
2
、氧、硫或硫的氧化形式;Z 是 (a)、(b)、(c) 或 (d),其中 R
1
是氢、羟基、卤素、C
1-3
烷氧基,任选被取代,任选含有一个或多个杂原子,饱和或不饱和,支链或直链 C
1-5
烷基,最好是甲基,可选择被取代,可选择含有一个或多个杂原子 C
5-8
环烷基、任选取代的芳基或杂芳基或任选取代的苄基;以及 X 是(CH
2
)
m
-A-(CH
2
)
n
其中 m 和 n 相同或不同,且选自整数 0、1、2、3 或 4,A 是 CH═CH、C═C、CHB、C═O、任选取代的氮、氧、硫或任选氧化形式的硫,B 是氢、卤素、羟基、C
1-3
烷氧基或任选取代的甲基或其盐,与至少一种二羧酸酯酰化酶或其功能等同物接触,并在至少一种青霉素酰化酶或其功能等同物存在下与&bgr;-内酰胺抗生素侧链的前体反应。