The reaction of Ox-glycyl chloride with a chiral imine derived
from the combination of d-(R)-glyceraldehyde acetonide and protected d-threonine afforded
optically active, highly functionalized
cis-substituted β-lactams 11 and 12.
These β-lactams provide versatile intermediates for
the
syntheses of biologically important carbacephalosporins, isooxacephems,
and other multicyclic
β-lactams. Desilylation and oxidation of 12 with
Dess−Martin periodinane followed by intramolecular cyclization produced a novel tricyclic β-lactam 17
and a 1-(hydroxymethyl)-O-2-isocephem
18 with [6R,7R] absolute
configuration. Removal of the Ox protecting group and acylation of
17 in
a one-pot reaction followed by saponification furnished the target salt
24. Alternatively, reaction
of phthaloylglycyl chloride with the chiral imine derived from the
combination of l-(S)-glyceraldehyde
acetonide and protected d-threonine gave only one
enantiomeric azetidinone 27 in high yield.
Further manipulation of 27 provided a new tricyclic
β-lactam 39 with [6S,7S] absolute
configuration
which satisfies the stereochemistry typically required for
antibacterial activity. This synthetic
procedure provides a short, versatile and enantioselective method of
preparing polycyclic β-lactams.
Biological testing of these tricyclic β-lactams indicated that
salt 39 has potential inhibitory activity
against four typical strains of bacteria.
Stereocontrolled syntheses of two potent antiviral agents,
β-l-FD4C and β-l-FddC, were
accomplished both in 10-step sequences, with an overall yield of 27% and
25%, respectively. It is
worthwhile to mention that the introduction of a phenylseleno moiety to
the C-2α position of the
lactone 4 can now be performed in a stereocontrolled
fashion, providing the key intermediate 5α in
75% yield.
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