Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1995-07-06
1997-08-12
Shah, Mukund J.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
540215, 540222, C07D50136
Patent
active
056567553
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a process for preparing a 3-substituted cephem compound from an allenyl-.beta.-lactam compound which can be easily produced from an inexpensive penicillin compound by a simple reaction procedure.
The 3-substituted cephem compound prepared by the process of the present invention is useful as an antibacterial agent having a wide antibacterial spectrum (e.g., Japanese Unexamined Patent Publications Nos. 119593/1973, 37788/1986, 51688/1987, 211287/1988 and 313482/1989).
TECHNICAL BACKGROUND
Japanese Unexamined Patent Publication No.119593/1973 discloses a process for preparing a 3-substituted cephem compound by coupling a carbonyl compound with a 3-phosphoranilideneethyl cephalosporin compound derived from a 3-halogenomethyl cephalosporin compound.
Japanese Unexamined Patent Publication No.37788/1986 and. Helv. Chim. Acta, 57, 2024 (1974) disclose processes for preparing a 3-substituted arylmethyl cephem compound by coupling a 3-acetoxymethyl cephalosporin compound with a substituted benzene in the presence of a Lewis acid.
A typical process for preparing the 3-substituted cephem compound was reported which comprises subjecting to coupling reaction a 3-trifluorooxycephem (A) or a 3-chloromethylcephem (B) and an organotin compound in the presence of a palladium catalyst as illustrated below in a reaction scheme (J. Org. Chem., 55, 5833-5847, 1990): ##STR1##
However, the foregoing known processes all require an expensive starting material having a cephalosporin skeleton. The process shown above in the reaction scheme has the drawback, from a commercial viewpoint, of using a theoretical amount of a detrimental organotin compound and an expensive palladium catalyst.
On the other hand, attempts have been made to prepare a 3-substituted cephem compound from an inexpensive penicillin derivative. For example, a process is known which comprises reacting an allenyl-.beta.-lactam compound represented by the formula ##STR2## wherein R.sup.1 is a hydrogen atom, a halogen atom, an amino group or a protected amine group, R.sup.2 is a hydrogen atom, a halogen atom, a lower alkoxy group, a lower acyl group, a lower alkyl group, a lower alkyl group having a hydroxyl group or a protected hydroxyl group as a substituent, a hydroxyl group or a protected hydroxyl group, R.sup.3 is a hydrogen atom, or a carboxylic acid-protecting group, R.sup.4 is an aryl group optionally having a substituent or a nitrogen-containing aromatic heterocyclic group optionally having a substituent, and m is 0 or 2, namely the starting material used in the process of the invention, with a nucleophile represented by the formula wherein Y is a nucleophile residue, giving a 3-substituted cephem compound represented by the formula ##STR3## wherein R.sup.1, R.sup.2, R.sup.3 and Y are as defined above (Japanese Unexamined Patent Publication No.282387/1992). This process, however, can not produce the contemplated compound of the present invention because the compound of the formula (D) wherein Y is an alkenylmethyl group or arylmethyl group can not act as a nucleophile. The aforesaid publication teaches nothing about some features of the present invention such as the use of a specific metallic reducing agent and a specific organohalogen compound.
A technique for preparing a compound having a .beta.-lactam ring is disclosed, for example, in Japanese Unexamined Patent Publication No.211055/1992, the technique using lead, copper, titanium, bismuth, antimony or the like as a metallic reducing agent along with a metal such as aluminum, zinc, magnesium, tin or the like which have a higher ionization tendency than said metallic reducing agent. Stated more specifically, the publication discloses a process comprising reacting a halogenated .beta.-lactam compound represented by the formula ##STR4## wherein R.sup.a is an amino group or a protected amino group, R.sup.b is a hydrogen atom or a carboxyl-protecting group, R.sup.c is a hydrogen atom or a hydroxyl-protecting group, and Ar is an aryl group optionally having a s
REFERENCES:
patent: 5266691 (1993-11-01), Farino et al.
Journal of the Chemical Society, Chemical Comm., No. 12, 21 Jun. 1994; Tanaka et al., pp. 1461-1462.
Cram & Hammond, "Organic Chemistry" 2nd Edition 1962, pp. 565-567.
Sasaoka Michio
Shiroi Takashi
Tanaka Hideo
Torii Shigeru
Otsuka Kagaku Kabushiki Kaisha
Shah Mukund J.
Sripada Pavanaram K.
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