Optically active azetidinones

Details Optically active azetidinones Optically active azetidinones

1988-08-18

1990-07-03

Lee, Mary C.

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C07D40504

Patent

active

049392484

DESCRIPTION:

BRIEF SUMMARY
DESCRIPTION

1. Technical Field
This invention relates to novel 3-substituted azetidinone compounds, and more specifically, to compounds represented by the following formula ##STR3## wherein Y represents an acetyl, 1-hydroxyethyl or 1-fluoroethyl group, R.sub.1 represents a hydrogen atom or an easily splittable amino-protecting group, and R.sub.2 and R.sub.3 are identical or different and each represents a hydrogen atom, a lower alkyl group, a phenyl group, a benzyl group or a diphenylmethyl group, or R.sub.2 and R.sub.3 together represent a lower alkylene group.
2. Background Art
3-Substituted azetidinone derivatives, particularly 3-substituted azetidinone derivatives having an S-configuration at the 4-position, are useful as intermediates for the production of various antimicrobial beta-lactam compounds such as carbapenem and carbapenem antibiotics, and various types of azetidinone derivatives have been previously proposed.


DISCLOSURE OF THE INVENTION

The present inventors have now found that 3-substituted azetidinone derivatives having an S-configuration at the 4-position represented by the above formula (I) can be stereo selectively obtained by using relatively inexpensive D-mannitol as a starting material, and reacting a ketal compound of D-glyceraldehyde derived from the starting material with diketene in the presence of a certain azole compound. This discovery has led to the accomplishment of the present invention.
The compounds of formula (I) provided by this invention are useful as synthesis intermediates for various medicines, particularly carbapenem or carbapenem antibiotics, for example an antibiotic of the following formula which is known to have excellent antimicrobial activity and relatively good stability to kidney dehydropeptidase. ##STR4##
The term "lower", as used in this specification to qualify a group or a compound, means that the group or compound so qualified has not more than 8 carbon atoms, preferably not more than 6 carbon atoms.
The "easily splittable amino-protecting group" includes amino-protecting groups that can be eliminated from compounds, to which they are bonded, by hydrolysis, reduction, oxidation, or otherwise without substantially affecting the other functions of the compounds adversely. Examples are tri(lower alkyl)silyl groups such as trimethylsilyl and tert-butyldimethylsilyl; a benzyl group which may be substituted by one or two lower alkoxy groups, such as benzyl, methoxybenzyl and dimethoxybenzyl; and a phenyl group which may be substituted by one or two lower alkoxy groups, such as methoxyphenyl and dimethoxyphenyl.
The "lower alkyl group" may be linear or branched, and includes, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl and tert-butyl.
The "lower alkylene group" preferably has 4 to 5 carbon atoms as in tetramethylene and pentamethylene.
The hydroxyl group and the fluorine atom in 1-hydroxyethyl and 1-fluoroethyl groups represented by Y in formula (I) may take either an S- or an R-configuration. In general, the fluorine atom desirably takes an R-configuration.
Typical examples of the compounds of formula (I) provided by this invention include -2-azetidinone, 4-methoxy)phenyl-2-azetidinone, -methoxy)phenyl-2-azetidinone, -methoxy)phenyl-2-azetidinone, none, l]-2-azetidinone, thyl]-2-azetidinone, hyl]-2-azetidinone, 4-yl]-2-azetidinone, yethyl]-2-azetidinone, 3-dioxolan-4-yl]-2-azetidinone, R)-1-fluoroethyl]-2-azetidinone, ]-2-azetidinone, oxolan-4-yl]-2-azetidinone, zyl-2-azetidinone, 1-(4-methoxy)benzyl-2-azetidinone, -azetidinone, )-hydroxyethyl]-2-azetidinone, rimethylsilyl-2-azetidinone, dioxolan-4-yl-2-azetidinone, ]-2-azetidinone, l-2-azetidinone, and .
A compound of formula (I) in which Y represents an acetyl group can be produced, for example, by reacting a compound represented by the following formula ##STR5## wherein R.sub.1, R.sub.2 and R.sub.3 are as defined hereinabove, with diketene of the following formula ##STR6## in the presence of an azole compound represented by the following formula ##STR7## wherein A re

REFERENCES:
Matsunoga et al., "Tetrahedron Letters", vol. 24, No. 29, pp. 3009-3012 (1983).

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