1,2-Amino Alcohols and Their Heterocyclic Derivatives as Chiral Auxiliaries in Asymmetric Synthesis

Glycoproteins, glycolipids, and glycophospholipids (glycoconjugates) are components of membranes. The oligosaccharide residue is responsible for intercellular recognition and interaction; it acts as a receptor for proteins, hormones, and viruses and governs immune reactions. These significant activities have stimulated interest in oligosaccharides and glycoconjugates. With their help it should be possible to clarify the molecular basis of these phenomena and to derive new principles of physiological activity. Major advances in the synthesis of oligosaccharides have been made by the use of the Koenigs-Knorr method, in which glycosyl halides in the presence of heavy-metal salts are employed to transfer the glycosyl group to nucleophiles. The disadvantages of this procedure have led to an intensive search for new methods. Such methods will be discussed in this article. Emphasis is placed on glycoside and saccharide formation by 1-O-alkylation, on the trichloroacetimidate method, and on activation through the formation of glycosylsulfonium salts and glycosyl fluorides.

New Methods for the Synthesis of Glycosides and Oligosaccharides—Are There Alternatives to the Koenigs‐Knorr Method? [New Synthetic Methods (56)]

The Henry reaction: recent examples

The addition of C-nucleophiles such as Grignard reagents or enolates to chiral α- or β-alkoxy aldehydes or ketones creates a new center of chirality and is therefore diastereogenic. In order to control stereoselectivity, two strategies have been developed: (1) Use of Lewisacidic reagents which form intermediate chelates, these being attacked stereoselectively from the less hindered side (chelation control); (2) use of reagents incapable of chelation, stereoselective attack being governed by electronic and/or steric factors (non-chelation control). Generally, the two methods lead to the opposite sense of diastereoselectivity. It is possible to predict the outcome by careful choice of organometallic reagents containing elements such as Li, Mg, B, Si, Sn, Cu, Zn, or Ti.

For corrigendum see DOI:10.1002/anie.198407461

Chelation or Non‐Chelation Control in Addition Reactions of Chiral α‐ and β‐ Alkoxy Carbonyl Compounds [New Synthetic Methods (44)]

Neuropharmacological Mechanisms of Nerve Agent-induced Seizure and Neuropathology

Formation of convenient chiral intermediates from carbohydrates and their use in synthesis

Phosphorus stereochemistry : Mechanistic implications of the observed stereochemistry of bond forming and breaking processes at phosphorus in some 5- and 6-membered cyclic phosphorus esters

The configurations of the cis- and trans-isomers of 2-substituted 1,3,2-oxazaphospholidin(e)-2-ones, -2-thiones, and 2-selones derived from (–)-ephedrine have been established by spectroscopic and chemical methods. Displacements of the exocyclic 2-substituents occur with retention of configuration at phosphorus. With sodium alkoxides, the 1,3,2-oxazaphospholidine ring is opened by P–N rather than P–O bond cleavage, and inversion of configuration at phosphorus is observed. Under basic conditions the 2-methylamino-1-phenylpropyl phosphates derived from (–)-ephedrine rearrange to afford aziridines and phosphoric acid derivatives; in the cases of the sulphur- and selenium-containing derivatives optically active phosphorus thioacids and phosphorus selenoacids are formed and can be isolated as SMe and SeMe derivatives. These latter derivatives are converted into O-alkyl derivatives on treatment with alcohols in the presence of alkoxides or bromine or silver nitrate, and the stereoselectivities of these reactions have been determined. The optical purities of the title compounds have been measured by an n.m.r. method using chiral shift reagents.

1,3,2-Oxazaphospholidines from (–)-ephedrine. Intermediates for the stereospecific synthesis of optically active dialkyl alkylphosphonothioates and -selenoates, trialkyl phosphoro-thioates and -selenoates, dialkyl methylphosphonates, and trialkyl phosphates

Asymmetric synthesis: Part I. A stereoselective synthesis of benzylic centres. Derivatives of 5-C-phenyl-d-gluco-pentose and 5-C-phenyl-l-ido-pentose

Five procedures have been used to compare the pharmacological effects and time-activity profiles of anti-acetylcholine drugs in the central and peripheral nervous system (ens, pns). In particular, the potencies of optically pure enantiomers of anti-acetylcholine drugs which contain an asymmetric centre have been determined. The following four observations are made which are of relevance to all studies of anti-acetylcholine drugs. (1) Times to onset of activity of anti-acetylcholine drugs in three in vivo tests and the duration of action in one in vivo test are shown to increase as affinity constants, determined in vitro, increase. (2) Below a dose of ca 0.03 μmol kg−1no anti-acetylcholine drug produces maximum mydriatic effects and all anti-acetylcholine drugs which have log affinity constant values >9.49 produce maximal effects at approximately this dose. (3) The receptor with which anti-acetylcholine drugs interact is essentially the same in the eye, salivary gland and ens of the mouse, the guinea-pig ileum, and in the cat ens. (4) For any anti-acetylcholine drug the time to onset of effects in the ens is similar to the time of onset of effects in the pns and appears to depend on the affinity constant rather than on the partition properties of the drug. The practical and theoretical significance of these and other observations are discussed.

Thomas D. Inch

Papers

Formation of convenient chiral intermediates from carbohydrates and their use in synthesis

Phosphorus stereochemistry : Mechanistic implications of the observed stereochemistry of bond forming and breaking processes at phosphorus in some 5- and 6-membered cyclic phosphorus esters

1,3,2-Oxazaphospholidines from (–)-ephedrine. Intermediates for the stereospecific synthesis of optically active dialkyl alkylphosphonothioates and -selenoates, trialkyl phosphoro-thioates and -selenoates, dialkyl methylphosphonates, and trialkyl phosphates

Asymmetric synthesis: Part I. A stereoselective synthesis of benzylic centres. Derivatives of 5-C-phenyl-d-gluco-pentose and 5-C-phenyl-l-ido-pentose

The central and peripheral activities of anti-acetylcholine drugs. Some concepts of practical relevance.