W. V. Murray

Bio: W. V. Murray is an academic researcher. The author has contributed to research in topics: Steroid & Total synthesis. The author has an hindex of 1, co-authored 2 publications receiving 18 citations.

Steroids. 2. Synthesis of C-18 functionalized steroids via the Smith-Hughes route.

Abstract: The total synthesis of a series of racemic C-18 functionalized steroids was carried out in a search for novel estrogen-and/or progestin-receptor agonists or antagonists. The target compound 3,18-dihydroxyestra-1,3,5(10)-triene (2), 13-(2-oxopropyl)gona-4-en-3-one (3), 13-(1-hydroxy-1-prop-2-ynyl)gona-4-en-3-one (4a and 4b) and 13-(1-acetoxy-2-oxo-1-propyl)gona-4-en-3-one (5) are position isomers of the highly biologically active estradiol, progesterone, norethindrone, and 17-acetoxyprogesterone, respectively. Nevertheless the synthetic C-18 functionalized steroids 3-5 showed little activity in the Clauberg and anti-Clauberg assays. Compound 2 showed no antagonism in the postcoital assay despite the fact that it exhibited weak but measurable in vitro receptor-binding activity.

Steroids. 2. synthesis of c-18 functionalized steroids via the smith-hughes route

Abstract: The total synthesis of a series of racemic C-18 functionalized steroids was carried out in a search for novel estrogen-and/or progestin-receptor agonists or antagonists. The target compound 3,18-dihydroxyestra-1,3,5(10)-triene (2), 13-(2-oxopropyl)gona-4-en-3-one (3), 13-(1-hydroxy-1-prop-2-ynyl)gona-4-en-3-one (4a and 4b) and 13-(1-acetoxy-2-oxo-1-propyl)gona-4-en-3-one (5) are position isomers of the highly biologically active estradiol, progesterone, norethindrone, and 17-acetoxyprogesterone, respectively. Nevertheless the synthetic C-18 functionalized steroids 3-5 showed little activity in the Clauberg and anti-Clauberg assays. Compound 2 showed no antagonism in the postcoital assay despite the fact that it exhibited weak but measurable in vitro receptor-binding activity.

Selective optimization of side activities: another way for drug discovery.

Abstract: The SOSA (selective optimization of side activities) approach is reviewed. It's an alternative to high-throughput screening for drug discovery

Incorporation of an Intramolecular Hydrogen-bonding Motif in the Side-Chain of 4-Aminoquinolines Enhances Activity against Drug-Resistant P. falciparum

Abstract: Previous data showing that several chloroquine analogues containing an intramolecular hydrogen-bonding motif were potent against multidrug-resistant P. falciparum led to the exploration of the importance of this motif. A series of 116 compounds containing four different alkyl linkers and various aromatic substitutions with hydrogen bond accepting capability was synthesized. The series showed broad potency against the drug-resistant W2 strain of P. falciparum. In particular, a novel series containing variations of the alpha-aminocresol motif gave eight compounds with IC50 values more potent than 5 nM against the W2 strain. Such simple modifications, significantly altering the pKa and sterics of the basic side chain in chloroquine analogues, may prove to be part of a strategy for overcoming the problem of worldwide resistance to affordable antimalarial drugs.

Asymmetric Diels-Alder Reactions of Unsaturated β-Ketoesters Catalyzed by Chiral Ruthenium PNNP Complexes

Abstract: Cyclic α-unsaturated β-ketoesters undergo cycloaddition with di- and trisubstituted butadienes to give tetrahydro-1-indanone derivatives with up to 93% ee in the presence of a ruthenium catalyst formed by activation of [RuCl2(PNNP)] with (Et3O)PF6 (2 equiv) (PNNP = (1S,2S)-N,N′-bis[o-(diphenylphosphino)benzylidene]cyclohexane-1,2-diamine). The protocol has been used to prepare the estrone derivative (8R,13S,14S)-13-tert-butoxycarbonyl-3-methoxy-7,8,12,13,15,16-hexahydro-6H-cyclopenta[a]phenanthren-17(14H)-one as a single diastereoisomer with 85% yield and 99% ee after one crystallization step. Its absolute configuration, which has been determined by X-ray diffraction after reduction to the alcohol and esterification with camphanic chloride, is in agreement with the attack of the diene onto the open enantioface of the β-keto ester (O−O) in the ruthenium complex [Ru(O−O)(PNNP)]2+, whose X-ray structure has been determined.

Ruthenium complexes with chiral tetradentate PNNP ligands: Asymmetric catalysis from the viewpoint of inorganic chemistry

Abstract: This is a personal account of the application of ruthenium complexes containing chiral tetradentate ligands with a P2N2 ligand set (PNNP) as catalyst precursors for enantioselective “atom transfer” reactions. Therewith are meant reactions that involve bond formation between a metal-coordinated molecule and a free reagent. The reactive fragment (e.g. carbene) is transferred either from the metal to the non-coordinated substrate (e.g. olefin) or from the free reagent (e.g. F+) to the metal-bound substrate (e.g. β-ketoester), depending on the class of catalyst (monocationic, Class A; or dicationic, Class B). The monocationic five-coordinate species [RuCl(PNNP)]+ and the six-coordinate complexes [RuCl(L)(PNNP)]+ (L = Et2O, H2O) of Class A catalyse asymmetric epoxidation, cyclopropanation (carbene transfer from the metal to the free olefin), and imine aziridination. Alternatively, the dicationic complexes [Ru(L–L)(PNNP)]2+ (Class B), which contain substrates that act as neutral bidentate ligands L–L (e.g., β-ketoesters), catalyse Michael addition, electrophilic fluorination, and hydroxylation reactions. Additionally, unsaturated β-ketoesters form dicationic complexes of Class B that catalyse Diels–Alder reactions with acyclic dienes to produce tetrahydro-1-indanones and estrone derivatives. Excellent enantioselectivity has been achieved in several of the catalytic reactions mentioned above. The study of key reaction intermediates (both in the solid state and in solution) has revealed significant mechanistic aspects of the catalytic reactions.

The Birch Reduction of Aromatic Compounds

Abstract: The reduction of aromatic compounds by alkali metals in liquid ammonia represents an important method for the preparation of partially unsaturated six-membered rings. The reaction was discovered by Wooster and Godfrey, but the major development resulted from the efforts of A. J. Birch, and the reaction has since come to bear his name. Although a variety of metals can be used, the most common are sodium and lithium, and, to a lesser extent, potassium. Cosolvents such as ether or tetrahydrofuran (THF) are often used to improve solubility, and weak acids such as alcohols may be employed during the reaction as proton sources. The latter are necessary for the reduction of benzene and its unactivated derivatives. Improvement in experimental procedures by Wilds and Nelson, the application to polynuclear compounds by Huckel and later by Harvey, and the development of methods for the alkylation of the anions generated in this process (i.e., reductive alkylation) have made this reaction an important approach to the synthesis of a wide variety of organic compounds. Keywords: Birch reduction; regiochemistry; mechanisms; stereochemistry; intramolecular effects; polynuclear aromatic compounds; aryl ethers; aromatic ketones; aromatic carboxylic acids; aromatic carboxylic esters; aromatic amides; phenols; aromatic amines; arylsilanes; bond cleavage; dimerization; Benkeser reduction; silylation; electrochemical reductions; catalytic hydrogenation; method comparisons; experimental procedures; scope; limitation