Metalloporphyrins as chemical mimics of cytochrome P-450 systems

Abstract: Certain synthetic metalloporphyrins have been shown to mimic the in vivo metabolism of some pharmaceuticals. Oxidation, hydroxylation and N-demethylation yielded synthetic metabolites. If found to be general, this lays the foundation of a predictive basis to optimize analog design of inhibitors with reduced oxidative reactivity, to determine the proclivity of drugs to form biologically active metabolites and provides a convenient methodology for their preparation

Drug Discovery Development

xvii, 380 hal.; ill.; 23c

Drug discovery and development / edited by Mukund S. Chorghade.

pharmacy bookfair2016Includes bibliographical references and index.v.1

A carbohydrate-based approach for the total synthesis of strictifolione

A chiral pool approach starting with d-glucose, using the Yamaguchi protocol and a Z-selective HWE reaction followed by lactonization, has been applied to execute the total synthesis of strictifolione

A short and efficient synthetic strategy for the total syntheses of (S)-(+)-and (R)-(−)-plakolide A

Concise and efficient total syntheses of anticancer agents (S)-(+)-Plakolide A and (R)-(−)-Plakolide A were accomplished in eight steps and an overall yield of 39% starting from geraniol. The key steps in our strategy are Sharpless asymmetric epoxidation, double elimination, and Stille coupling reactions

<span style="font-size:12.0pt;font-family: "Times New Roman";mso-fareast-font-family:"Times New Roman";mso-ansi-language: EN-GB;mso-fareast-language:EN-US;mso-bidi-language:AR-SA" lang="EN-GB">Stereoselective bioreduction of chalcone and β-diketone by <i style="mso-bidi-font-style:normal">Saccharomyces cerevisiae</i> in biphasic solvent system: A mechanistic study</span>

992-1001<span style="font-size:12.0pt;font-family: " times="" new="" roman";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-gb;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="" lang="EN-GB">&nbsp;A mechanistic study of steroselective bio-reduction of chalcones and β-diketones to their corresponding hydroxy derivatives with an effective and versatile biocatalyst <i style="mso-bidi-font-style: normal">i.e. Saccharomyces cerevisiae (Baker’s yeast) in different biphasic solvents systems have been carried out. Maximum bioreduction was observed in pet. ether-water (60% v/v), chloroform-water (60% v/v) for compound (R)-3-(5-chloro-2-hydroxyphenyl)-3-hydroxyl-1-phenylpropane-1-one 2a and (R)-3-(5-methyl-2-hydroxyphenyl)-3-hydroxyl-1-phenylpropane-1-one 2b, respectively while ethanol-water (80%v/v) for 4-chloro-2- ((R, <i style="mso-bidi-font-style: normal">E)-1-hydroxy-3-phenyl allyl) phenol <b style="mso-bidi-font-weight: normal">4a. These biphasic systems are instrumental in integrating bioconversion and product recovery in a single system and shifting the chemical equilibrium to enhance yield and selectivity.</span

A practical synthesis of (R)-(&#8722;)-phenylephrine hydrochloride

(R)-(&#8722;)-Phenylephrine hydrochloride is a clinically potent adrenergic agent and B-receptor sympathomimetic drug, exclusively marketed in the optically active form. An asymmetric synthesis has been developed with high enantiomeric excess based on hydrolytic kinetic resolution of a styrene oxide derivative using (R,R)-SalenCoIIIOAc complex

A novel and simple asymmetric synthesis of CMI-977 (LDP-977): A potent anti-asthmatic drug lead

A practical gram scale asymmetric synthesis of CMI-977 is described. A tandem double elimination of an α-chlorooxirane and concomitant intramolecular nucleophilic substitution was used as the key step. Jacobsen hydrolytic kinetic resolution and Sharpless asymmetric epoxidation protocols were applied for the execution of the synthesis of the key chiral building block

Stereoselective synthesis of (2S, 7S)-7-(4-phenoxymethyl)-2-(1-N-hydroxyureidyl-3-butyn-4-yl) oxepane: a potential anti-asthmatic drug candidate

We have achieved a short, efficient stereoselective synthesis of 7-membered oxepane derivatives with potential against asthma. Highlights of our synthetic strategy are regioselective oxidation of a hydroxyl group and efficient ring closure of an open chain aldehyde to a 2-benzenesulfonyl oxepane derivative with PhSO2H. Surprisingly the cis-isomer showed better activity than the trans-isomer