Chwang Siek Pak

Magnesium-methanol as a simple convenient reducing agent for α,β -unsaturated esters

Abstract Various α, β -unsaturated esters undergo double bond reduction by magnesium in methanol to give the corresponding saturated ones in almost quantitative yields.

The Current Status and Future Perspectives of Studies of Cannabinoid Receptor 1 Antagonists as Anti-Obesity Agents

Since the discovery of rimonabant (Acomplia: 1), a large effort has been directed at the discovery of new, potent and selective CB(1)R antagonists that serve as anti obesity drugs. As a result, a number of compounds reached various stages of clinical trials by late 2008. However, the announcement by Sanofi-Aventis that they were discontinuing all ongoing trials with rimonabant, as a result of the finding that risks associated with depression and anxiety outweighed its benefits, had a major impact on this area. A wave of terminations of programs targeting the development of CB(1)R blockers for treatment of obesity ensued. However, abandoning this CB(1)R therapeutic target for anti-obesity drug development seems to be premature, since there are a number of potential approaches have been uncovered to circumvent the problems of the current agents. In this review, we summarize advances that have been made and the status of studies of a diverse array of CB(1)R antagonists that have been identified mainly based on modifications of the first-in-class CB(1)R antagonist, rimonabant. Various approaches have been employed to design these analogs, such as bioisosteric replacement, introduction of conformational constraints, scaffold hopping and ligand-based molecular modeling. In addition, current approaches that have been uncovered to avoid psychiatric side effects of CB(1)R antagonists are summarized. Finally, the design of non-brain penetrating and peripherally acting CB(1)R antagonists, allosteric modulators of CB(1)R, and neutral antagonists for CB(1)R is also discussed in this review.

An efficient desulfonylation method mediated by magnesium in ethanol

Abstract An extremely convenient desulfonylation method of primary, secondary, tertiary alkyl and vinyl phenyl sulfones was developed by using magnesium in ethanol in the presence of catalytic amount of mercuric chloride to give the corresponding alkanes and alkene in almost quantitative yields.

Facile transformation of 3,4-disubstituted 2-azetidinones to chiral 5,6-dihydro-2-pyridones

Abstract Chiral 5,6-disubstituted-5,6-dihydro-2(1 H )-pyridones were prepared efficiently from readily accessible 3,4-disubstituted-2-azetidinones having preadjusted substituents and stereochemistry through the reductive ring opening of 2-azetidinones followed by Z -selective installation of acetate moiety and re-cyclization to 2-pyridones.

An efficient Julia olefination mediated by magnesium in ethanol

Abstract Reductive elimination step of Julia olefination was conveniently achieved by using magnesium powder in absolute ethanol in the presence of catalytic amount of mercuric chloride at room temperature to give the corresponding alkenes in almost quantitatively yields.

Facile conversion of 2-azetidinones to 2-piperidones: application to a formal synthesis of Prosopis and Cassia alkaloids

Abstract Nonracemic 5,6-disubstituted 2-piperidones were prepared from readily accessible 3,4-disubstituted-2-azetidinones having pre-installed substituents by reductive ring opening of 2-azetidinones followed by stereoselective installation of Z-α,β-unsaturated ester and lactam formation. For the synthetic application to the naturally occurring piperidine alkaloids, such as Prosopis and Cassia alkaloids, 5-hydroxy-2-piperidones (+)-13 and (−)-24 were prepared from 2-azetidinones (−)-6b and (+)-18 via two-carbon ring homologation.

Asymmetric borane reduction of ketones catalyzed by oxazaborolidine

Abstract Asymmetric reduction of prochiral ketones with borane-methyl sulfide (BMS) in the presence of chiral oxazaborolidine( 3 ) afforded the corresponding secondary alcohols in moderate to high (46–97%) optical yields.

Facile transformation of 2-azetidinones to unsaturated ketones: application to the formal synthesis of sphingosine and phytosphingosine

Azetidinones were smoothly transformed to unsaturated ketones through the ring opening of activated 2-azetidinone by phosphonate stabilized carbanion and subsequent Horner-Wadsworth-Emmons olefination of the resulting -ketophospho- nates with aldehydes. A formal synthesis of L-erythro-sphingosine and D-lyxo-phytosphingosine from readily available 2-azetidi- none was established utilizing this methodology.

An efficient deoxygenation of 1-alkenyl or alkyl phenyl sulfoxides to the corresponding sulfides mediated by magnesium in alcohol

Abstract An extremely convenient deoxygenation of 1-alkenyl, alkyl, and aryl phenyl sulfoxides with magnesium powder in absolute methanol (or ethanol) afforded the corresponding sulfides in excellent yields.

Reaction of thioamides with zinc enolate: Synthesis of vinylogous carbamates

Abstract Eschenmoser sulfur extrusion reaction is failed to produce vinylogous carbamate II from N-( t -Boc)pyrrolidine-2-thion I but, treatment of methyl bromozincacetate with N-( t -Boc)pyrrolidine-2-thion I afforded good yield of vinylogous carbamate II . This thio-Reformatsky reaction appeared to be sensitive to the structure of substrates i.e. ring size or N-protecting groups.