Synthesis of α-trifluoromethyl-α-amino-β-sulfone hydroxamates: novel nanomolar inhibitors of matrix metalloproteinases

The racemic α-trifluoromethyl-α-amino-β-sulfone hydroxamates 1 were synthesized by means of a nucleophilic addition of sulfur-stabilized carbanions to a N-Cbz imine of trifluoropyruvate (4). The free amino derivative 1a was the most potent inhibitor of both MMP-3 (stromelysin-1) and MMP-9 (gelatinase-B), showing an IC₅₀ = 14 nM and 1 nM, respectively, and excellent selectivity versus MMP-1 (>5000-fold difference in inhibitory capacity). The N-Me derivative 1b was the most selective for MMP-3 with respect to MMP-9 (62-fold difference).     

Synthesis of α-amino-β-hydroxy acids using N,N-bis(trimethylsilyl)aminoketene bis(trimethylsilyl) acetal or its N-methyl-N-trimethylsilyl analog

Condensation of the title compounds with aldehydes and ketones in the presence of trimethylsilyl triflate provided the corresponding α-amino-β-hydroxy acids in fair to good yields as a mixture of diastereomers.     

Synthesis of α-hydroxy(polyprenyl) bisphosphonates

Bisphosphonates derived from natural terpenes were synthesized by phosphonylation of corresponding aldehydes. The general strategy of introduction of the phosphonate groups into the polyprenol molecule involves successive treatment of a hydroxyl compound by Swern reagent to oxidize the C-OH group into C=O and a (EtO)₃P/[PyH]⁺ClO _? ⁴ mixture to phosphylate the resulting carbonyl compound.     

Synthesis and structural study of α-amino- and α,ω-diamino oligoamides-11

α-Amino (MAO) and α,ω-diamino (DAO) oligoamides were prepared using dodecylamine or 1,6 diaminohexane as a chain limitator. These were characterized by GPC, ¹H-NMR and ¹³C-NMR; molecular models: N-dodecyldodecanamide and 1,6 bis dodecylaminohexane; trifluoroacetylation was used to dissolve the oligoamides. DAO prepared in the melt contains two types of chains, depending on the position of the limitator. When oligomers were prepared in solution using the Yamazaki method, the presence of residual phosphorus derivatives in the oligoamides could not be avoided.     

Synthesis of new derivatives of α-mangostin (microreview)

Chemistry of Heterocyclic Compounds - This microreview presents the current state of research on functionalization of α-mangostin, a natural hydroxyxanthone. Examples of transformations are...     

Synthesis of α-Diketones from α,β-Dihydroxy Ketones

Treatment of α,β-dihydroxy ketones with carbonyldiimidazole resulted in the formation of α-diketones based on the elimination of the cyclic carbonates formed in situ.     

Synthesis of Heterocycles Based on α,β-Unsaturated P(III) Derivatives

Abstract

A general method of phosphorus heterocycle synthesis has been developed. It is based on the interaction between α,β-ethylene, acetylene P(III) derivatives and reagents, which contain electrophilic and nucleophilic centres in α,β- and α,β-positions, e.g. compounds with activated multiple bonds; β-halogenalcanols and thiols; nitrilimines, nitrilylides as 1,3-dipoles. This process is an unsynchron-ic ionic cycloaddition which begins with the attack of a phosphorus atom to the electrophilic centre of a reagent.     

Analytical techniques for the detection of α-amino-β-methylaminopropionic acid

The non-protein amino acid L-α-amino-β-methylaminopropionic acid (BMAA) has been linked to several neurodegenerative diseases. Its presence in trace amounts in complex sample such as bacterial, plant and mammalian tissue extracts and hydrolyzates makes analysis a complicated process requiring good analytical technique. There are conflicting reports in the literature regarding the presence or absence of BMAA in key samples, but the absence of standardized or validated methods makes comparison of the disparate findings difficult to compare. This critical review will summarize the historic and recent literature, and provide suggestions for improving the methods currently in practice.     

Synthesis of α-Cyano-β-fluoro-α-hydroxyesters

The ring opening fluorination of glycidic gem-cyanoesters was achieved by action of pyridine polyhydrofluoride at 25°C in dichloromethane. The regioselective nucleophilic substitution reaction allows the synthesis of a new class of fluorohydrins with OH, CN and CO₂R on the same carbon atom.     

Synthesis of (Methyl-β-cyanoethyl)cyclosiloxanes

Previously unknown (methyl--cyanoethyl)tri-, -tetra-, and -pentacyclosiloxanes were prepared by oxygen-halogen exchange between silicon and tin. The ²⁹Si NMR spectra of the products were measured and interpreted.     

Synthesis and Stereochemistry of α-Aryl-β-Nitroalkylphosphinate

Abstract

Twenty-three new α -aryl-β -nitroalkylphosphinates 3a - g were synthesized in high yields under very mild conditions. Compounds 3 consist of two pairs of diastereomeric isomers (A) and (B)     

A highly efficient method for the α,β-dehydrogenation of α-amino esters and α-amino-β-diesters

N-monochlorination of N-unprotected α-amino esters and α-amino-β-diesters was efficiently and very simply effected by using inexpensive effervescent sodium dichloroisocyanurate tablets for water disinfection in a biphasic organic solvent-water system. Subsequent dehydrochlorination provided α,β-didehydroaminoacid esters, whose hydrogenation would allow the starting compounds to be easily racemized.     

Synthesis of α-alkyl- and α,α-dialkyl-β-phenyltryptamines

A new method was developed for the synthesis of -alkyl- and ,-dialkyl--phenyltryptamines based on alkylation of nitroalkanes with -phenyl-nor-gramine.     

Stereoselective Synthesis of (E) or (Z) α-Alkenylphosphonates via α-Stannylated Phosphonates

α-lithiostannylalkylphosphonates react with aldehydes with the complete elimination of the organotin moiety. The stereoselective formation of the (E) or (Z) α-alkenylphosphonates is closely dependent on the tin substituent.     

Synthesis of esters of α-chloroacetoxy-β,β,β,-trichloroethylphosphonic acids

Summary The synthesis of 11 previously unreported dialkyl esters of -mono-, -di-, and -trichloroacetoxy-,,-trichloroethylphosphonic acids has been effected.     

Copper (I) Iodide-Catalyzed Solvent-Free Synthesis of α-Aminophosphonates

Abstract

A method for the synthesis of α-aminophosphonates through the three-component coupling reaction of aldehydes, amines, and diisopropyl phosphite using copper (I) iodide salt catalyst is demonstrated, The reaction is highly efficient, economic, and also environment friendly.

[Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental resource: Table S1, Figures S1–S9.]

GRAPHICAL ABSTRACT      

Stereoselective allylation reactions of acyclic and chiral α-amino-β-hydroxy aldehydes

Stereoselective allylation reactions of acyclic and chiral α-amino-β-hydroxy aldehydes affording chiral β-amino-α,γ-diols are described. Several Lewis acids (BF₃·OEt₂, SnCl₄, TiCl₄, ZnCl₂, and MgBr₂·OEt₂) were employed to mediate the allylation reactions. The reactions of anti-α-NHCbz-β-OTBS substrates mediated by SnCl₄ afforded syn-selective products. The same reaction conditions also gave satisfactory results for the reactions of syn-α-NHCbz-β-OTBS substrates. The mechanism involves α-chelation between the amido group and aldehyde oxygen.