Synthesis of Methyl α-D-Kijanoside

Abstract

In 1981, Mallams and coworkers reported¹ the discovery of - D-kijanose 1, a branched-chain nitro sugar, isolated from the antitumor antibiotic kijanimicin by acid hydrolysis. The structure of this unusual carbohydrate was established ^1,2 as 2,3,4,6-tetadeo xy-4 - (methoxy carbony1 amino 1-3-c-methyl - 3 -nitro - D-xylo-hexopyranose by spectroscopic and crystallographic analysis, and comparison with D-rubranitrose 2, a carbohydrate found in the antibiotic rubradirin .³Two other nitro sugars, L-evernitrose 3 and - L-decilonitrose 4⁵, have been discoveredas components of antibiotics.     

Phase Transfer Catalysed Synthesis of Methyl α-Bromomethylacrylate

Methyl α-bromomethylacrylate 1 is an important intermediate both as a starting material for specifically functionalized polymers and for use in general organic synthesis. As an example of the former it has been used to prepare polymeric anthraquinoid dyes¹. Synthetically, its bifunctional reactivity towards nucleophilic attack has made it useful in the preparation of both spiro² and bicyclic^3,4 ring systems. Several reports of synthetic methods leading to α-methylenelactones, having potential antitumor activity, have also been reported which use α-bromomethylacrylate as a starting point⁵.     

Copper Catalyzed ATRP of Methyl Methacrylate Using Aliphatic α-Bromo Ketone Initiator

The atom transfer radical polymerization (ATRP) of MMA was examined using 3-bromo-3-methyl-butanone-2 (MBB) as an initiator in the presence of CuBr as catalyst and 2,6-bis[1-(2,6-diisopropylphenylimino)ethyl]pyridine (BPIEP) as a tridentate N-donor ligand. The effect of various other N-donor ligands including a bisoxazoline ligand, namely, 2,6-bis(4,4-dimethyl-2-oxazolin-2-yl) pyridine (dmPYBOX) was studied in ATRP and reverse ATRP of MMA. The ATRP of MMA in toluene at 90 °C using MBB as initiator was relatively slow in the case of bidentate and faster in the case of tridentate N-donor ligands. The apparent rate constant, k_app, with MBB as initiator and BPIEP as ligand in toluene (50%, v/v) at 90 °C was found to be 7.15 × 10⁻⁵ s⁻¹. In addition, reverse ATRP of MMA in diphenylether at 70 °C using BPIEP/CuBr₂ as catalyst system was very effective in reducing the reaction time from several hours to 24 h for polymerization of MMA.     

Stereocontrolled Conversion of Allylic Alcohols Into Vicinal Cis-Diols: New Syntheses of Methyl α-L-Digitoxoslde and Methyl 2-Deoxy-α-L-Fucoside

A synthetic process is outlined in which an allylic alcohol is converted into its primary urethane derivative, which is then subjected to iodonium ion induced cyclization to give a single iodo-carbonate. The carbonate is then deiodinated reductively and hydrolyzed to afford the vicinal diol. By use of this process the two title sugars have been prepared from methyl 2.3.6-trideoxv-α-L-ervthro-hex-2-enopvranoside and its α-L-threo counterpart.     

Free-Radical Copolymerization of Methyl Methacrylate and α-Methacrylophenone. I. Reactivity Ratios

The free-radical copolymerization of methyl methacrylate and methacrylophenone (MAP) initiated by azobisisobutyroni-trile at 60°C has been studied in ethylbenzene solution and in bulk. The process is characterized by a competitive Diels-Alder condensation of methacrylophenone and by a very low reactivity of methacrylophenone-terminated macroradicals in propagation reactions. The experimental composition data are consistent with a terminal unit model: r_A = 1.77 ± 0.02, r_B = 0.110 ± 0.006. Copolymerization with depropagation of methacrylophenone-terminated growing chains and copolymerization affected by penultimate effects have been tested as optimized possible models to take into account the inability of MAP to undergo homopolymerization.     

Solid-phase Synthesis of Diethyl Trans-1-Aklenephosphonates Using Polymer-bound α-Diethoxyphosphoryl Methyl Selenide

Polymer-supported organic reagents have been applied to the rapid preparation of smallorganic molecules because they can provide attractive and practical methods forcombinatorial chemistry and solid-phase synthesis1. Vinylphosphonates bearing anelectron withdrawing groups at the α-position are versatile intermediates for the synthesisof some hetero- and carbocyclic compounds2. Many methods have been developed forpreparing their parent compounds, 1-alkenephosphonates. Among those methods, anim…     

Coupling of Methyl Ketones and Primary or Secondary Amines Leading to α-Ketoamides

A metal-free oxidative coupling of methyl ketones and primary or secondary amines to α-ketoamides has been developed. Four intermediates, α-iodoketone, α-aminoketone, iminium intermediate, and α-hydroxy amine have been identified through a series of control experiments. The atom-economic methodology can be scaled-up, tolerates a variety of functional groups, and is operationally simple.     

Solid-phase Synthesis of Diethyl Trans-1-Alkenephosphonates Using Polymer-bound α-Diethoxyphosphoryl Methyl Selenide

The solid-phase preparation of diethyl trans-l-alkenephosphonates via seleno-polymer reagent has been reported.     

Synthesis of Methyl 2,6-Dideoxy-3-C-Methyl-α-D-ribo- hexopyranoside (Methyl α-D-Mycaroside), a Component of the Antitomor Agent Mithramycin

Methyl α-D-mannopyranoside (4) was converted into methyl 2,6-dideoxy-3-C-methyl-ct-D-ribo-hexopyranoside (20) (methyl α-D-mycaroside) by an efficient sequence of reactions (Schemes 1 and 3). A similar set of reactions also was used to convert L-rhamnose (2) into methyl α-L-mycaroside (21). Attempted synthesis of methyl 2,6-diseoxy-3-C-methyl-a-D-arabino-hexopyranoside (22) (methyl α-D-olivomycosidej from methyl 6-deoxy-3-C-methyl-4-O-(2,2-dimethylpropanoyl)～2-O-trif lyl-α-D-arabino-hexopyranoside (18), a compound generated during～synthesis of 20, was thwarted by a methyl migration which produced methyl 2,6-dideoxy-2-C-methyl-α-D-ribo-hexopyranoside (23).     

Kinetic Resolution of DL-Phenylalanine Methyl Ester by α-Chymotrypsin Immobilized on Porous Silica Beads

PreparationofL-phenylalanineisAnportantforthemanufacturingofthesyntheticsweetener,AspartaIne.Manyschemeshavebeendevelopedforthepreparation.Oftheseschemes,theprepimionviairnInobilizeda-chymotwsinenZymaticstereoselectivehydrolysisoftheL-phenylalaninemethylesterinDL-estersolutionshowedsuperiority['].However,theenZyIneboobiliZationsupport,Sepharose,isveryexpensiveandsoft,andishardtobehandledonaconunercialscale.Wehavenotedthatporoussilicabeadswasakindofrigid,cheaP,easilyavailableenZytnedriobi…     

Atom Transfer Radical Polymerization of Methyl Methacrylate with α,α-Dichlorotoluene or α,α,α-Trichlorotoluene as Initiator

lnAtomTransferRadicalPolymerization(ATRP),whichisanew"living"/contr0lledradicalp0lymerizati0ntechniquedevel0pedindependentlybyMatyjaszewskieIallandSawam0t0eIaP,anyalkyIhalidewithactivatedsubstituents0na-carbonsuchasaryl,carb0nyl0rallylcanbeusedasinitiatoe.Benzy1haIideandpolymerswithbenzylhalideendgr0upwerereportedtobeefficientinitiator0rmacroinitiatorfortheATRPofstyrene".H0wever,whenbenzylhalidewasusedt0initiateMMAp0Iymerization,itwasfoundthattheinitiationefficiencywasveryIowinourlabo…     

Tetrazoles: XLVI. Alkylation of 5-Substituted Tetrazoles with Methyl Chloromethyl Ether and α-Methylstyrene

Alkylation of 5-aryl(hetaryl)tetrazoles with methyl chloromethyl ether under conditions of phase-transfer catalysis leads to formation of isomeric 1- and 2-methoxymethyltetrazoles at a ratio of ~1 : 2. The reaction of 5-substituted tetrazoles with -methylstyrene in the presence of trichloroacetic acid gives the corresponding 2-(,-dimethylbenzyl)tetrazoles in high yield and with high regioselectivity.     

Solvolysis of 1-Chloro-1-Alkenyl Phenyl Sulfides. Synthesis of α-Bromo Phenyl Thiocarboxylic Esters, α-Bromo Alkyl Carboxylic Esters and α-Phenylthio Methyl Carboxylic Esters

1-chloro-1-alkenyl phenyl sulfides treated with bromine followed by hydrolysis or methanolysis give α-bromo phenyl thiocarboxylic esters and α-phenyl-thio methyl carboxylic esters. Direct oxidative solvolysis with bromine and alcohol give α-bromo alkyl carboxylic esters.     

The α-Effect and Competing Mechanisms: The Gas-Phase Reactions of Microsolvated Anions with Methyl Formate

The enhanced reactivity of α-nucleophiles, which contain an electron lone pair adjacent to the reactive site, has been demonstrated in solution and in the gas phase and, recently, for the gas-phase S_N2 reactions of the microsolvated HOO^–(H₂O) ion with methyl chloride. In the present work, we continue to explore the significance of microsolvation on the α-effect as we compare the gas-phase reactivity of the microsolvated α-nucleophile HOO^–(H₂O) with that of microsolvated normal alkoxy nucleophiles, RO^–(H₂O), in reactions with methyl formate, where three competing reactions are possible. The results reveal enhanced reactivity of HOO^–(H₂O) towards methyl formate, and clearly demonstrate the presence of an overall α-effect for the reactions of the microsolvated α-nucleophile. The association of the nucleophiles with a single water molecule significantly lowers the degree of proton abstraction and increases the S_N2 and B_AC2 reactivity compared with the unsolvated analogs. HOO^–(H₂O) reacts with methyl formate exclusively via the B_AC2 channel. While microsolvation lowers the overall reaction efficiency, it enhances the B_AC2 reaction efficiency for all anions compared with the unsolvated analogs. This may be explained by participation of the solvent water molecule in the B_AC2 reaction in a way that continuously stabilizes the negative charge throughout the reaction.

Improved Synthesis and Resolution of α-N-Benzoyl-β(3-Qumolyl)-DL-α-Alanine Methyl Ester

The title compound has been synthesized and resolved previously by T. M. Kubiak. In our searching of new potent agonists of LH-RH(luteinizing hormone releasing hormone), α-N-t-butyloxycarbonyl-β-3-quinolyl)-D-α-alanine and its L-isomer were synthesized. The unprotected.optically active amino acids were obtained by enzymatic hydrolysis of the title compounds, followed by hydrolysis in 6 mol/L hydrochloric acid. The title compound was synthesized initially with 3-quinolinecar-     

Reformatsky Reaction of Methyl α-Bromoisobutyrate with Schiff Bases Derived from Salicylaldehyde and 2-Hydroxynaphthalene-1-carbaldehyde

Reformatsky reaction of methyl -bromoisobutyrate with Schiff bases derived from salicylaldehyde and its analogs gives the corresponding 1,4-disubstituted 3,3-dimethylazetidin-2-ones.     

Radical Polymerization and Copolymerization of Methyl α-(Fluoroalkoxymethyl)acrylates and Characterization of Their Polymers

Abstract

Representatives of a new type of fluorine-containing monomer, methyl α-(fluoroalkoxymethyl)acrylates (MCFMA's), were prepared. The fluoroalkoxy groups introduced were OCH₂CF₃, OCH₂CF₂CF₂H, and OCH(CF₃)₂. All the monomers synthesized readily polymerized to number-average molecular weights of 55,000 to 110,000 at a 2 mol/L monomer concentration in dioxane using 5 × 10^?3 mol/L of 2,2′-azobisisobutyronitrile at 60°C. The polymerization rate tended to decrease slightly with an increase in the size of the alkoxy group. Copoly-merization of MCFMA's with styrene revealed that the fluoroalkoxy-methyl group functions as an electron-attracting group depending on the number of fluorine atoms. According to thermogravimetric analysis, poly(MCFMA)'s were thermally less stable than poly(methyl methacrylate). Greater contact angles of the polymers from MCFMA's with water than poly(methyl methacrylate) were observed.     

Phosphine-Catalyzed Sequential Michael Addition between α-Aminonitriles and Methyl Acrylate for Cyclization: Synthesis of N-Aryl-Substituted Pyrrolidines

Russian Journal of Organic Chemistry - N-Aryl-substituted pyrrolidine derivatives were synthesized via tributylphosphine-catalyzed sequential Michael addition of α-aminonitriles and methyl...     

Liquid-Phase Synthesis of Methyl (2Z)-2-Arylsulfonylmethyl-2- alkenoates from PEG-Supported α-Phenylselenopropionate

Treatment of lithio derivative of novel PEG-supported a-phenylselenopropionate with aldehydes, followed by oxidation-elimination with 30% hydrogen peroxide, formed Baylis-Hillman products, which were then reacted with sodium arylsulfinate. The resulting sulfonylated products were cleaved from the PEG efficiently affording methyl (2Z)-2-arylsulfonylmethyl-2-alkenoates in good yields and high purities.     

1,3-Dipolar Addition of Methyl α-Diazoacetoacetate to Enamines： A New Synthetic Route to 5-Amino-4,5-dihydrofurans

The reaction of methyl α-diazoacetoacetate with enamines catalyzed by dirhodium and copper complexes underwent formal 1,3-dipolar addition to give 5-amino-4,5-dihydrofurans in moderate yields. The reaction was suggested to proceed via a nucleophilic addition of enamines to rnetal-carbenes and a subsequent intramolecular cyclization of the resulting zwitterionic intermediates.