-
14
-
-
84914088221
-
Recents Advances in the Chemistry of β-Lactam Antibiotics
-
P.H. Bentley, R. Southgate, Roy. Soc. Chem, London, Ch. 6
-
(1989)
Spec. Pub. No. 70
-
-
Bachi1
-
18
-
-
84914088220
-
-
The only report that makes use of a terminal alkyne group as a pro-radical center in the β-lactam series was by Bachi who recently described the synthesis of some bicyclic β-lactams starting from 4-alkynyl-β-lactams through a one-pot, four-step, sequential reaction. See:
-
-
-
-
20
-
-
84914088219
-
-
The interest in carbapenams rests in their structural similarity to the carbapenem-type compounds, highly active, broad-spectrum, antibiotics with β-lactamase resistence. For reviews on the synthesis of carbapenem, see:
-
-
-
-
28
-
-
84914088218
-
-
2-Azetidinones 3 were prepared according to Bose's procedure for the synthesis of glyceraldehyde acetonide derived β-lactams:
-
-
-
-
30
-
-
84914088217
-
-
Compounds 1b-d were obtained as mixtures of E/Z isomersacross the double bond having the same cis-configuration in the β-lactam ring.
-
-
-
-
31
-
-
84914088216
-
-
3SnH (1.15 mmol), and AIBN (0.1 mmol) was refluxed in dry benzene (20 mL) under an argon atmosphere, until complete disappearance of the starting substrate (t.l.c.). The solvent was evaporated in vacuo to give an oil which was purified by flash chromatography. In all the cases, major isomer was eluted first. In some cases partial destannylation and/or decomposition was observed, specially in the 6-alkoxycarbapenams. Complete separation and/or purification of both diastereomers was not possible in these cases. All pure compounds gave satisfactory spectroscopic and analytical data.
-
-
-
-
32
-
-
84914088215
-
-
It is notable that radical cyclization to give carbapenams 2 occurs under standard conditions while related processes developed to prepare bicyclic β-lactams do not occur except in high dilution conditions. See, for example ref. 3. In our case, good yields of compounds 2 were obtained even when working in the absence of solvent (neat conditions).
-
-
-
-
34
-
-
84914088214
-
-
To determine the nature of both isomers obtained in the cyclization of 2-azetidinones 1 (epimers at C1 or E/Z isomers in the olefinic double bond), the isolated isomers of compound 1a were treated with TsOH. Two new carbapenams, 4a, lacking the tin moiety were obtained. Therefore, both isomers of 2a should have the same stereochemistry in the double bond but are epimers at C1. Moreover, according with previous background (see ref. 1) for cyclization of enynes it may be assumed that the double bond has a Z-stereochemistry.
-
-
-
-
35
-
-
84914088213
-
-
The same yield and stereochemical result was obtained starting both with a mixture of E/Z-1c (85/15) and pure isomer Z-1c.
-
-
-
-
36
-
-
84914088116
-
-
1,5 = 8.0 – 8.7 Hz. Therefore, relative configuration at C1 could not be unambiguously established from NMR data.
-
-
-
-
40
-
-
84914088115
-
-
Methodologies based on Pd and other organometallic reagents to functionalize performed bicyclic β-lactam systems have experienced an explosive growth during the last years. For a recent review on functionalization of bicyclic β-lactams using organometallic methodologies, see:
-
-
-
-
41
-
-
33751038771
-
The Development of Organometallic Methodologies For the Stereospecific Introduction of Cephalosporin Side Chains
-
(1994)
Synlett
, pp. 565
-
-
Farina1
Kant2
-
42
-
-
84914088114
-
-
For a very recent report on palladium mediated cross coupling of a penem stannane, see:
-
-
-
|
