David C. Rees

Solid-phase organic reactions: A review of the recent literature

Abstract Combinatorial chemistry has emerged as a powerful new technology for chemists to synthesise large numbers of compounds for biological evaluation. One of the techniques used in combinatorial chemistry is polymer supported or “solid-phase” organic synthesis. This article reviews the main chemical reactions reported between 1992-October 1995 using solid-phase support, focusing upon those suitable for synthesising small molecules. The reactions are presented in graphical format in a table according to reaction types. Examples presented include amide bond formation, aromatic substitutions, condensations, cycloadditions, diazotisation, enzymatic coupling, use of Grignard reagents, Michael additions, multiple component reactions, nucleophilic substitution, olefination, oxidations, protection/deprotection, reduction, immobilisation and cleavage. Finally, the information presented is evaluated briefly and some trends are discussed.

Solid-phase organic reactions II: A review of the literature Nov 95–Nov 96

Abstract This Report reviews literature published Nov 1996–Dec 97; it is the third in a series that summarises organic reactions performed on solid supports and is designed as an update to Tetrahedron Reports no. 394 and 418. The reactions are presented in a graphical abstract format and examples are given of the following reactions: amide formation, aromatic substitution (nucleophilic/electrophilic), cleavage, condensation, cycloaddition, deprotection/protection, Grignard and related reactions, heterocycle formation, immobilisation onto resin, Michael addition, miscellaneous, multiple component condensation, olefin formation, oxidation, reduction and substitution (nucleophilic/electrophilic). Solid-phase peptide or other oligomer synthesis and reactions using soluble polymeric supports are not included. This report ends with the discussion of some trends in the domain under consideration. This report summarises literature published during Nov 96 – Dec 97 describing solid-phase organic reactions.

A novel linker strategy for solid-phase synthesis

Abstract The REM resin for solid phase synthesis is described. Its use is illustrated by preparing a small array of tertiary amines using a Hofmann elimination reaction. No functional group is required for linking these compounds onto the resin other than the amine constructed during the synthesis.

Resin-immobilised benzyl and aryl vinyl sulfones: New versatile traceless linkers for solid-phase organic synthesis

Abstract New polystyrene-based resins containing benzyl and aryl vinyl sulfone groups are described. The vinyl sulfone group reacts efficiently with 2° amines, via conjugate addition, and the resin-bound 3° amine products can be quatermised through alkylation. Subsequent deamination to give 3° amines and the regenerated vinyl sulfone occurs in moderate to good yield. Both systems can be recycled and show moderate stability to acids and high stability to nucleophiles including Grignard reagents.

Synthesis of an array of amides by aluminium chloride assisted cleavage of resin-bound esters

A new method for the synthesis of amino amides using Wang or Tentagel-PHB resins is described. The method uses aluminium chloride to promote the conversion of resin-bound benzylic esters to amides under ambient conditions. The reactions were monitored in ‘real-time’ using 13C gel phase NMR.

Anionic cyclophanes as potential reversal agents of muscle relaxants by chemical chelation.

A series of carboxyl-containing cyclophanes have been designed and synthesised as chemical chelators (or host molecules) of cationic muscle relaxant drugs (or guest molecules). Three of these cyclophane derivatives, 1-3, have been shown by NMR to form 1:1 complexes with the muscle relaxants pancuronium, and gallamine, in D(2)O, with association constants up to 10(4) M(-1). When tested in an in vitro chick biventer muscle preparation, the cyclophanes reversed the neuromuscular block induced by pancuronium and gallamine, with having the most effective reversal against pancuronium (EC(50) 40 microM.

Chapter 5. Drugs in Anesthetic Practice

Publisher Summary This chapter discusses the recent research and development of anesthetic drugs. Drugs used in anesthetic practice comprise three main classes: hypnotics, muscle relaxants, and analgesics. From the earliest days has been a continual search for better anesthetic agents. Rapid induction by the intravenous route is the most popular method today, but the maintenance of anesthesia has by contrast, remained largely dependent upon the inhalation of gases. Recently, gaseous agents with very low blood solubilities have been developed that provide excellent control over the depth of anesthesia. Skeletal muscle relaxants (neuromuscular blockers, NMBs) are used widely in the clinic particularly to paralyze laryngeal muscles prior to airway intubation and also to paralyze other skeletal muscles before general surgery. All currently used muscle relaxing drugs in surgery today achieve their effect by blocking the physiological effects of acetylcholine at nicotinic acetylcholine receptors (nAChR) on the muscle. The analgesic properties of opioid agonists comprise one of the three key components of surgical anesthesia. In addition, they have intrinsic hypnotic properties and may reduce the requirement for other general anesthetics. Previous research into the pharmacology of opioid receptors has led to the identification of at least three G-protein coupled opioid receptor subtypes, designated mu, kappa, and delta. In addition to opioids, N 2 O is widely used in anesthetic practice; particularly for its analgesic properties. Local anesthetics are particularly popular for regional surgery and outpatient surgery where they offer a less complicated and less expensive alternative to general anesthesia. Many local anesthetics are used clinically as racemic mixtures. Research and development of new drugs has been characterized by a trend toward identifying fast onset, short duration compounds, with rapid patient recovery characteristics and minimal side-effect profiles that offer opportunities to reduce health care costs.