Two types of the carbapenem key intermediates (4 and 6) have been efficiently synthesized from inexpensive (S)-ethyl lactate (7). Thus, (S)-2-benzyloxypropanal readily obtainable from 7 was condensed with di-p-anisylmethylamine to give the chiral imine. The [2+2]-cycloaddition reaction of diketene with the imine underwent in a highly stereoselective manner, yielding the desired 3,4-trans-3-acetyl-β-lactam (13a) as a major product (diastereoselectivity 7∼10:1). This was elaborated to 4 and 6 in 9 and 6 steps, respectively.
All Science Journal Classification (ASJC) codes
- Drug Discovery
- Organic Chemistry