P-lactam synthon method

II. HIGHLY EFFICIENT SEMISYNTHESIS OF PACLITAXEL AND DOCETAXEL BY MEANS OF THE P-LACTAM SYNTHON METHOD... 

Our strategy was to apply the P-Lactam Synthon Method (P-LSM)47-49 developed in these laboratories for (i) the asymmetric synthesis of the (2 R,3 S)-N-ben-zoyl-3-phenylisoserine moiety with excellent enantiomeric purity in high yield, and (ii) the ring-opening coupling of A-acyl-P-lactams with DAB (3). 

The second chapter addresses new facets of the medicinal chemistry of the important anticancer drug Taxol (paclitaxel). Ojima and coworkers explore, in particular, the structure-activity relationship associated with the 3-phenylisoserine side chain, synthetically exploiting their P-Lactam Synthon Method . Their research has led to, among other things, a series of noteworthy second-generation taxoid anticancer agents. 

Ojima, I. Asymmetric syntheses by means of the P-lactam synthon method. Adv. in Asymmetric Synth. 1995,1, 95-146. 

Ojima, I. (1995) Recent advances in P-lactam synthon method. Accounts of Chemical Research, 28, 383-389. 

Since the advent of penicillin, p-lactam antibiotics have occupied a central role against pathogenic bacteria. Moreover, more and more novel p-lactam antibiotics (Figure 4.3) have been developed due to bacterial tolerance and resistance. Special impetus for research efforts on p-lactam chemistry has been provided by the introduction of the p-lactam synthon method, a term coined by Ojima over 15 years ago, according to which 2-azetidinones can be employed as useful intermediates in organic synthesis. 

Ojima I (1993) /9-Lactam Synthon Method Enantiomerically Pure /9-Lactams as Synthetic Intermediates. In Georg GI (ed) The Organic Chemistry of /9-Lactams. VCH Publishers, Inc., New York, p 197... 

P-Lactams have been used as a synthon for the preparation of a vast array of compounds. It has been reported that the reduction of 4-(haloalkyl)azetidin-2-ones with LiAlhL is a powerful method for the synthesis of stereodefined aziridines and azetidines <06OL1101>. However, reduction of 4-(haloalkyl)azetidin-2-ones with chloroalane afforded 2-(haloalkyl)azetidines, which were rearranged to 3,4-cw-disubstituted pyrrolidines and piperidines 32 <060L1105>. During these rearrangements, bicyclic azetidinium intermediates were formed which were ring opened by halides. The synthesis of a peptide-... 

---