Synthon method

This discussion is separated into three sections depending on whether fluorine, or polyfluoroalkyl group, is introduced into a heterocycle or whether the heterocycle is formed from fluorinated synthons. Methods of introduction of fluorine into N-containing heterocyclic compounds have been reviewed (90CLY959). 

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 Lactam Synthon Method, Adv. Asymm. Synth., Vol. I, Hassner, A., Ed., JALGreenwich, CT, 1995. 

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

Ojima, I., Kuduk, S. D., Slater, J. C., et al. (1996) Syntheses of new fluorine-containing taxoids by means of (i-lactam synthon method. Tetrahedron, 52, 209-24. 

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

Ojima, I., Habus, I., Zhao, M., et al. (1992) New and efficient approaches to the semisynthesis of taxol and its C-13 side-chain analogs by means of beta-lactam synthon method. Tetrahedron, 48, 6985-7012. 

Ojma I, Delaloge F (1997) Asymmetric synthesis of bmlding-blocks for peptides and pepti-domimetics by means of the -lactam synthon method. Chem Soc Rev 26 377-386... 

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... 

Ojima I (1995) Recent Advances in the /9-Lactam Synthon Method. Acc Chem Res 28 383... 

Ojima I, Sun CM, Zucco M, Park YH, Duclos O, Kuduk S (1993) A Highly Efficient Route to Taxotere by the / -Lactam Synthon Method. Tetrahedron Lett 34 4149... 

Ojima I, Kuduk SD, Slater JC, Gimi RH, Sun CM (1996) Syntheses of New Fluorine-Containing Taxoids by Means of /5-Lactam Synthon Method. Tetrahedron 52 209... 

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. 

By the early 1990s, de novo syntheses of the paclitaxel side-chain and methods for coupling it (/3-lactam synthon method) with the baccatin III system had been published . 

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