Penams, synthetic routes

Scheme 63 illustrates another synthetic route leading to the penam ring system (78JA4597). lis sequence contains some interesting points of synthetic strategy which are discussed in... 

Early syntheses of the alkylidene and heterocyclylmethylene penems were lengthy and produced racemic compounds [94, 95]. For BRL 42715 (31), a synthetic route was established which (i) utilized the inexpensive and readily available chiral synthon, 6-APA (8) as starting material, (ii) retained the (5R) stereochemical integrity of 6-APA and as much of the original penam framework as possible, (iii) introduced the C-6 substituent at a late stage in the synthetic sequence, and (iv) was amenable to large scale preparation (Scheme 6.17) [96, 97]. 

The previously described penem syntheses from 6-APA-derived starting materials have been inefficient in the sense that the C(2) and C(3) atoms of the penam are lost during the sequence. Scheme 71 shows a route in which C(2) and C(3) of the penam become C(2) and C(3) of the penem (79CC665). The major product of this sequence is the (55) enantiomer. A related synthetic approach, starting with the natural product clavulanic acid, has been described (79CC663). 

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