Divergent Stereochemical Outcomes in the Insertion of Donor/Donor Carbenes into the C–H Bonds of Stereogenic Centers

Intramolecular C–H insertions with donor/donor dirhodium carbenes provide a concise and highly stereoselective method to set two contiguous stereocenters in a single step. Herein, we report the insertion of donor/donor...

A convenient stereoselective method for synthesis of β-lactams under microwave irradiation with [BmIm]OH as a reusable ionic liquid.

: A promoted synthetic protocol for the β-lactams synthesis in the presence of [BmIm]OH as a basic reagent under microwave irradiation [M.W.I.] is described. The reaction was highly diastereoselective. In all cases, this protocol provided trans-β-lactams as major isomers, and β-lactams were obtained with good yields. Further, the effect of the order of addition of the reagents was particularly investigated; we found that this order is very important. The best results are obtained when the imine is added gradually. This work shows that [BmIm]OH is an advantageous recyclable basic reagent. A qualitative molecular orbital diagram is illustrated to interpret the observed diastereoselectivity.

Biomimetic approach to the catalytic enantioselective synthesis of tetracyclic isochroman

Polyketide oligomers containing the structure of tetracyclic isochroman comprise a large class of natural products with diverse activity. However, a general and stereoselective method towards the rapid construction of this structure remains challenging due to the inherent instability and complex stereochemistry of polyketide. By mimicking the biosynthetic pathway of this structurally diverse set of natural products, we herein develop an asymmetric hetero-Diels–Alder reaction of in-situ generated isochromene and ortho-quinonemethide. A broad range of tetracyclic isochroman frameworks are prepared in good yields and excellent stereoinduction (up to 95% ee) from readily available α-propargyl benzyl alcohols and 2-(hydroxylmethyl) phenols under mild conditions. This direct enantioselective cascade reaction is achieved by a Au(I)/chiral Sc(III) bimetallic catalytic system. Experimental studies indicate that the key hetero-Diels-Alder reaction involves a stepwise pathway, and the steric hindrance between in-situ generated isochromene and t-Bu group of Sc(III)/N,N’-dioxide complex is responsible for the enantioselectivity in the hetero-Diels–Alder reaction step.

NbCl5-Mg Reagent System in Regio- and Stereoselective Synthesis of (2Z)-Alkenylamines and (3Z)-Alkenylols from Substituted 2-Alkynylamines and 3-Alkynylols

The reduction of N,N-disubstituted 2-alkynylamines and substituted 3-alkynylols using the NbCl5–Mg reagent system affords the corresponding dideuterated (2Z)-alkenylamine and (3Z)-alkenylol derivatives in high yields in a regio- and stereoselective manner through the deuterolysis (or hydrolysis). The reaction of substituted propargylamines and homopropargylic alcohols with the in situ generated low-valent niobium complex (based on the reaction of NbCl5 with magnesium metal) is an efficient tool for the synthesis of allylamines and homoallylic alcohols bearing a 1,2-disubstituted double bond. It was found that the well-known approach for the reduction of alkynes based on the use of the TaCl5-Mg reagent system does not work for 2-alkynylamines and 3-alkynylols. Thus, this article reveals a difference in the behavior of two reagent systems—NbCl5-Mg and TaCl5-Mg, in relation to oxygen- and nitrogen-containing alkynes. A regio- and stereoselective method was developed for the synthesis of nitrogen-containing E-β-chlorovinyl sulfides based on the reaction of 2-alkynylamines with three equivalents of methanesulfonyl chloride in the presence of stoichiometric amounts of niobium(V) chloride and magnesium metal in toluene.

Obtaining new substituted 4-dimethylamino-2-(naphth-1-yl)-phenyl- 1-(2-chloroquinolin-3-yl)-butan-2-ol having activity against resistant strains of M. Tuberculosis

The discovery in 2002 among derivatives of 6-bromo-3-benzyl-2-methoxyquinolines the highly active compounds against M. Tuberculosis bacterium and its drug-resistant strains led to the creation of the innovative anti-TB drug TMS-207 in 2013 by Janssen-Cilag, Bedaqueline® (1R, 2S)*-1-(6-bromo-2-methoxy-3-quinolyl)-4-dimethylamino-2-(naphth-1-yl)-1-phenyl-butane-2-ol. Developing this area of research in our laboratory we set ourselves the task of further modifying the structure of Bedakvelin® in order to obtain new not described patent-capable compounds with greater bioavailability and fewer side effects. To achieve this goal, it was planned to synthesize a number of derivatives of TMS-207 with a change in the substituents in the quinoline ring. Among the structural analogues of Bedakvelin® described in the literature, derivatives of 2-chloroquinolines were absent. The synthesis and study of properties derived from this particular structure has become the goal of this study. It was decided to preserve as the active molecule fragment of the base part the Bedakvelin® which was optimal for derivatives of 2-methoxy-quinolinolin order. The scheme of obtaining the target compounds that we have chosen is practically uncontested if we take into account the boundary conditions for the cost of raw materials and minimize the number of synthesis stages. The resulting diastereomeric pairs differ in activity in M. Tuberculosis. RSSR diastereomeric pairs had greater activity against mycobacteria than RRSS diastereomeric pairs. Stereoselective or stereospecific preparation of such compounds with a good yield is desirable when producing the necessary tertiary alcohols. The aim of this work was to determine all the reaction conditions that affect the yield of the target 4-dimethylamino-2-(naphth-1-yl)-phenyl-1-(2-chloroquinolin-3-yl)-butan-2-ols, and the determination of the possibility of a stereospecific or stereoselective method for the synthesis of such compounds.

β-Selective xylulofuranosylation via a conformationally-restricted glycosyl donor

Reported is the first stereoselective method for β-xylulofuranosylation, which employs 3,4-O-xylylene-protected thioglycoside donors.

Tetrafluorobenzyl Alcohol-Oriented Novel (S)-Enantiomeric Esters: Synthesis and Structure-Activity Relationship

Background: Using constantly and widely chemistry insecticides has resulted in a selection burden and favored tolerance development in various insect species. Particularly, pyrethroids are the only one which can be used for net impregnation either ITNs or LLIN as yet, however, the excessive use of pyrethroids has led to many cases of insect resistance in worldwide. Therefore, it is urgent to develop novel insecticides fighting against this sort of resistance. Methods: Based on the preliminary studies, we explored a straightforward highly stereoselective method to achieve the novel chiral ester derivatives by using Oppolzer’s 10,2-camphorsultam as chiral controlling reagent. Results: A series of tetrafluorobenzyl alcohol oriented (S)-enantiomeric esters were designed and synthesized by the asymmetric synthesis. All the compounds exhibited moderate yields, and the original synthesized compounds have been evaluated for their potential insecticidal activity against Plutella xylostella compared with those of fenvalerate and D-trans-phenothrin, and some compounds presented excellent insecticidal activities. Conclusion: The bioassay illustrated that some of the compounds exhibit obviously insecticidal activities against Plutella xylostella, especially, the insecticidal activity of compound 5i was as good as commercial fenvalerate and D-trans-phenothrin, which can be used as a lead compound for further optimization.

Synthesis of N-substituted Five and Six-membered Iminocyclitols-bearing Sugar Moiety: Strategy Toward the Synthesis of Pseudodisaccharide

Aim and Objective: The efficient synthesis of disaccharide containing iminosugar moiety has a considerable interest in the field of glycoscience. In the present work, we describe a novel and applicable method for synthesis of five and six-membered N-substituted iminosugars attached with sugar moiety (pseudodisaccharides). Materials and Methods: The method of the glycosylation was based on the coupling of iminosugar thioglycoside (glycosyl donors) with partially protected sugars (glycosyl acceptors) in the presence of DMTST as a promoter. 2D COSY, HMQC, HMBC experiments were carried out to assist in NMR signal assignments. The pseudoanomeric configuration was established through NOE experiments and molecular modeling calculations. Results: Two classes of pseudodisaccharides were successfully obtained, five and six-membered N-substituted iminosugars glycosides. The six-membered pseudodisaccharides compounds were produced selectively with only β anomer. The corresponding five-membered pseudodisaccharides were achieved with moderate stereoselectivity. The yields obtained were good. These derivatives of iminocyclitols are thought to be precedents to develop various pseudodisaccharides, novel biologically active compounds, and new functional molecules. Conclusion: According to the results, utilizing iminosugar thioglycosides (1 and 2) as a glycosyl donor in glycosylation reactions is an efficient and highly stereoselective method to prepare (five- and six-membered) iminocyclitols (iminosugars) that bear a sugar moiety. The results will add to the synthesis of the iminosugars derivatives and contribute to make our approach among the few methods able to synthesize iminosugar glycosides.