Local anaesthetics chemistry

Leprosy, chemotherapy, 20 (1983) 1 Ligand-receptor binding, 23 (1986) 41 Linear free energy, 10 (1974) 205 5-Lipoxygenase inhibitors and their antiinflammatory activities, 29 (1992) 1 Literature of medicinal chemistry, 6 (1969) 66 Lithium, medicinal use of, 11 (1975) 193 Local anaesthetics, 3 (1963) 332 Lonidamine and related compounds, 21 (1984)111... 

Benzocaine is a local anaesthetic with a range of applications (see box). It is manufactured froitf toluene in a few steps using some quite simple chemistry. 

B H Takman and H J Adams, Local Anaesthetics In Medicinal Chemistry (Ed) M E Wolff (4th edn) New York, Wiley interscienee (1980). 

D Lednicer and L A Mitscher (Eds) Local Anaesthetics In The Organic Chemistry of Drug Synthesis, John Wiley and Sons, New York (1995). 

Knowledge of the chemistry of local anaesthetics also helps in finding possible substitutes, e.g., the replacement of an ester by an amide agent which neither cross-reacts, nor is likely to cause allergy by itself. Many other compounds have local anaesthetic properties, and may be thought of as potential alternatives, e.g., certain phenothiazine antihistamines and propranolol (the jS-adrenoceptor blocker). 

Phase-transfer catalysis is a vast area of organic chemistry, and there are many different examples of the applications of phase-transfer catalysts to asymmetric synthesis, particularly in the area of enantioselective a-ami-noacid synthesis. This area has been extensively reviewed by Maruoka, Lygo and O Donnell. However, there are limited examples where asymmetric phase-transfer catalysis has been applied to drug discovery. One notable example is the asymmetric allylation of glycine imine 337, catalysed by quaternary ammonium bromide 340, which has been used by Kumar et al, as the key step in the synthesis of local anaesthetic levobupivacaine " (339) (Scheme 14.102). 

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