Diane Mary Coe

Solid-supported reagents in organic synthesis.

The current interest in solid‐phase organic synthesis has led to a renewed interest in a complementary technique in which solid supported reagents are used in solution phase chemistry. This technique obviates the need for attachment of the substrate to a solid‐support, and enables the chemist to monitor the reactions using familiar analytical techniques. The purpose of this review is to increase awareness of the wide range of useful transformations which can be accomplished using solid‐supported reagents.

Inhibition of inducible nitric oxide synthase by acetamidine derivatives of hetero-substituted lysine and homolysine

The synthesis and in vitro evaluation of the acetamidine derivatives of hetero-substituted lysine and homolysine analogues have identified potent inhibitors of human nitric oxide synthase enzymes, including examples with marked selectivity for the inducible isoform.

α-Selective organocatalytic synthesis of 2-deoxygalactosides.

Alpha rules: A thiourea acts as an efficient organocatalyst for the glycosylation of protected galactals to form oligosaccharides containing a 2-deoxymonosaccharide moiety. The reaction is highly stereoselective for α-linkages and proceeds by way of a syn-addition mechanism.

Synthesis and Structure−Activity Relationships of Long-acting β2 Adrenergic Receptor Agonists Incorporating Metabolic Inactivation: An Antedrug Approach

A series of saligenin beta(2) adrenoceptor agonist antedrugs having high clearance were prepared by reacting a protected saligenin oxazolidinone with protected hydroxyethoxyalkoxyalkyl bromides, followed by removal of the hydroxy-protecting group, alkylation, and final deprotection. The compounds were screened for beta(2), beta(1), and beta(3) agonist activity in CHO cells. The onset and duration of action in vitro of selected compounds were assessed on isolated superfused guinea pig trachea. Compound 13f had high potency, selectivity, fast onset, and long duration of action in vitro and was found to have long duration in vivo, low oral bioavailability in the rat, and to be rapidly metabolized. Crystalline salts of 13f (vilanterol) were identified that had suitable properties for inhaled administration. A proposed binding mode for 13f to the beta(2)-receptor is presented.

Catalytic enantioselective cyclopropanation with bis(halomethyl)zinc reagents. I. Optimization of reaction protocol

Abstract The rate and selectivity of catalytic enantioselective cyclopropanation of cinnamyl alcohol utilizing bisiodomethyl zinc and 4a/4b is greatly dependent on the order of addition of the reagents. The independent preformation of the ethylzinc cinnamyloxide and bis(iodomethyl)zinc was found to be crucial. The reaction displayed autocatalytic behavior which was shown to be due to the generation of zinc iodide.

A 3,4‐trans‐Fused Cyclic Protecting Group Facilitates α‐Selective Catalytic Synthesis of 2‐Deoxyglycosides

A practical approach has been developed to convert glucals and rhamnals into disaccharides or glycoconjugates with high α-selectivity and yields (77–97 %) using a trans-fused cyclic 3,4-O-disiloxane protecting group and TsOH⋅H2O (1 mol %) as a catalyst. Control of the anomeric selectivity arises from conformational locking of the intermediate oxacarbenium cation. Glucals outperform rhamnals because the C6 side-chain conformation augments the selectivity.

Trityl ethers in oligosaccharide synthesis: A novel strategy for the convergent assembly of oligosaccharides

Abstract We have developed a novel glycosylation strategy in which a tritylated thioglycoside can act as a glycosyl donor and acceptor. In combination with previously reported chemoselective glycosylations, this feature enables highly convergent assembly of oligosaccharides

The chemistry of enoxysilacyclobutanes : highly selective, uncatalyzed aldol additions

O-(Silacyclobutyl) ketene acetals derived from esters, thiol esters, and amides reacted with a variety of aldehydes at room temperature without the need for catalysts. The O,O-ketene acetal of E-configuration reacted rapidly to afford the syn aldol products with high diastereoselectivity (93/7-99/1)

A simple method for the quantitative analysis of resin bound thiol groups

Abstract Non-aqueous solutions of Ellmans reagent [5,5′-dithio(2-nitrobenzoic acid), DTNB] can be used to quantify thiols supported on macroporous polystyrene and TentaGel resins. Organic solutions of Ellmans reagent may also be used as a qualitative tests for thiols on a wider range of solid supports.

Synthesis and Structure-Activity Relationships of Long-acting β2 Adrenergic Receptor Agonists Incorporating Arylsulfonamide Groups

A series of saligenin alkoxyalkylphenylsulfonamide beta(2) adrenoceptor agonists were prepared by reacting a protected saligenin oxazolidinone with alkynyloxyalkyl bromides, followed by Sonogashira reaction, hydrogenation, and deprotection. The meta-substituted primary sulfonamide was more potent than the para- and the ortho-analogues. Primary sulfonamides were more potent than the secondary and tertiary analogues. The onset and duration of action in vitro of selected compounds was assessed on isolated superfused guinea pig trachea. Sulfonamide 29b had the best profile of potency, selectivity, onset, and duration of action on both guinea pig trachea and human bronchus. Furthermore, 29b was found to have low oral bioavailability in rat and dog and also to have long duration of action in an in vivo model of bronchodilation. Crystalline salts of 29b were identified that had suitable properties for inhaled administration. A proposed binding mode for 29b to the beta(2)-receptor is presented.