Synthesis of N-(trifluorosilylmethyl)glutarimide. Alternate intramolecular coordination of the silicon atom to two oxygen atoms

A new representative of draconoids, N-(trifluorosilylmethyl)glutarimide, was synthesized by reaction of N-(trimethyoxysilylmethyl)glutarimide with boron trifluoride-ether complex. According to the IR and ¹H, ¹³C, ¹⁵N, ¹⁹F, and ²⁹Si NMR data, this compound molecule is characterized by intramolecular coordination between the silicon and carbonyl oxygen atoms (alternate coordination of the silicon atom to each oxygen atom).     

Chemical modification of L-glutamine to alpha-amino glutarimide on autoclaving facilitates Agrobacterium infection of host and non-host plants: A new use of a known compound

Background

Accidental autoclaving of L-glutamine was found to facilitate the Agrobacterium infection of a non host plant like tea in an earlier study. In the present communication, we elucidate the structural changes in L-glutamine due to autoclaving and also confirm the role of heat transformed L-glutamine in Agrobacterium mediated genetic transformation of host/non host plants.

Results

When autoclaved at 121°C and 15 psi for 20 or 40 min, L-glutamine was structurally modified into 5-oxo proline and 3-amino glutarimide (α-amino glutarimide), respectively. Of the two autoclaved products, only α-amino glutarimide facilitated Agrobacterium infection of a number of resistant to susceptible plants. However, the compound did not have any vir gene inducing property.

Conclusions

We report a one pot autoclave process for the synthesis of 5-oxo proline and α-amino glutarimide from L-glutamine. Xenobiotic detoxifying property of α-amino glutarimide is also proposed.     

Tetraoxo derivatives of perhydropyrrolo[3,4-c]pyridine

Michael adducts from diethyl fumarate with malonic esters or nitriles were cyclized to succinimide intermediates which, after glutarimide ring closure, afforded several N-methyl and N-benzyl derivatives of cis-1,3,4,6-tetraoxoperhydropyrrolo[3,4-c]pyridine whose configuration was demonstrated by X-ray crystal structure analysis.     

A new synthesis, including asymmetric synthesis, of spiro[4.n]alkenones from three components: cyclic ketones, chloromethyl p-tolyl sulfoxide, and acetonitrile; and a formal total synthesis of racemic acorone

1-Chlorovinyl p-tolyl sulfoxides were synthesized from several kinds of cyclic ketones and chloromethyl p-tolyl sulfoxide in good yields. Treatment of the 1-chlorovinyl p-tolyl sulfoxides with cyanomethyllithium at −78°C to room temperature gave spirocyclic enaminonitriles in high yields. Acidic treatment of the enaminonitriles afforded spiro[4.n]alkenones in good yields. By using an unsymmetrical cyclic ketone, α-tetralone, and optically active chloromethyl p-tolyl sulfoxide, this procedure afforded enantiomerically pure spiro[4.5]decenone in good yield with excellent asymmetric induction from the sulfoxide chiral center. By using this method a formal total synthesis of a racemic spirocyclic sesquiterpene, acorone, was realized.     

One-pot esterification and amidation of phenolic acids

We developed a new one-pot reaction of phenolic acids to afford the corresponding esters and amides through acyl-protected and activated phenolic acid intermediates. The simultaneous protection/activation of phenolic acids with alkylchloroformates proceeded readily in the presence of DMAP at room temperature; subsequent addition of alcohols or amines afforded the corresponding esters or amides. The use of iso-butyloxycarbonyl as the protecting and activating group in the one-pot reactions afforded phenolic esters or amides in 91% average yield. As a practical example of this convenient synthesis, caffeic acid phenethyl ester (CAPE) was readily synthesized from commercially available caffeic acid and phenethyl alcohol in 95% yield, and an isotopomer of CAPE, [3,10-¹³C₂]CAPE, was synthesized in 91% yield from [3-¹³C]caffeic acid and 2-[1-¹³C]phenethyl alcohol. This method may be useful for the convenient esterification and amidation of diverse phenolic acids.     

Synthesis and cytotoxicity study of pyrazoline derivatives of methoxy substituted naphthyl chalcones

2-Acetyl naphthalene reacts with various methoxy substituted benzaldehyde in the presence of 10 % sodium hydroxide solution giving functionalized chalcones. The synthesized chalcones when further reacted with hydrazine hydrate in the presence of acetic acid afforded N-acetyl pyrazolines. All the synthesized products were confirmed by various spectral data such as FTIR, ¹H NMR, ¹³C NMR, and HRMS studies. All the synthesized compounds were screened for cytotoxicity against various cell lines.     

Halogenation of <Emphasis Type="Italic">N</Emphasis>-substituted <Emphasis Type="Italic">p</Emphasis>-quinone monoimines and <Emphasis Type="Italic">p</Emphasis>-quinone monooxime ethers: XV. Synthesis and bromination of 4-(cinnamoyloxyimino)-cyclohexa-2,5-dienones

New 4-(cinnamoyloxyimino)cyclohexa-2,5-dien-1-ones were synthesized, and their bromination afforded bromine addition products to the syn- and anti-C=C bonds of the quinoid ring. In all cases, bromine addition to the C=C double bond of the cinnamoyl fragment was observed.     

Synthesis of 13a-methylphenanthroindolizidines using radical cascade cyclization: synthetic studies toward (±)-hypoestestatin 1

A radical cascade involving 6-endo cyclization of aryl radicals generated from N-acryloyl-N-(1-methylethenyl)-9-bromophenanthren-10-ylmethylamines, followed by 5-endo-trig cyclization of the resulting α-amidoyl radicals afforded phenanthroindolizidines bearing a methyl substituent at the angular C13a position. 2,3,6-Trimethoxy derivative was synthesized by using this method, but its spectral data were not in accord with those of literature values reported for hypoestestatin 1. Further synthetic study toward hypoestestatin 1 is demonstrated.     

A facile approach to spirocyclic butenolides through cascade cyclization/oxidative cleavage reactions of (Z)-enynols catalyzed by gold under dioxygen atmosphere

A facile approach for the syntheses of spirocyclic butenolides through cascade cyclization/oxidative cleavage reactions of (Z)-enynols bearing cyclic substituents at the C-1 position catalyzed by gold under dioxygen atmosphere has been developed. A variety of substituted butenolides was constructed in a regioselective manner from suitably substituted (Z)-2-en-4-yn-1-ols. (Z)-Enynols substituted both at C2 and C3-position afforded the spirocyclic butenolides in moderate to good yields, C-2 unsubstituted (Z)-enynols afforded the products in moderate yields, and the C-3 unsubstituted (Z)-enynols afforded the desired products in low yields.     

Ring-closing metathesis for the synthesis of 2H- and 4H-chromenes

Six 4H-chromenes were synthesized from substituted phenols using vinylstannylation and ring-closing metathesis (RCM) as key steps. In addition, a different approach involving amongst other steps, an aryl allyl isomerization and RCM afforded a set of seven 2H-chromenes from phenolic precursors.     

Novel optically active poly(amide-imide)s derived from L-aspartic acid

2,6-Bis-(2,5-dioxo-tetrahydro-N-(4-carboxyphenyl)pyrrol-3-yl)-pyrrolo[3,4-f]isoindole-1,3,5,7-teraone, a chiral diacid, was prepared from pyromellitic anhydride and L-aspartic acid in a three steps reaction pathway. The polycondensation reactions of the monomer with aromatic diamines were carried out in direct condensation reaction conditions. The synthesized poly(amide-imide)s had inherent viscosities in the range of 0.30–0.80 dl/g. Identification of all of the products were performed by conventional analytical techniques such as TLC, IR and ¹H NMR/¹³C MR spectroscopy. Thermoanalytical techniques (TGA/DSC) showed useful levels of thermal stability, associated with relatively high glass transition temperatures and carbonized residues in excess of 40% at 600°C for the synthesized polymers. Amorphous morphology was obtained based on XRD patterns and DSC traces. The polymers were soluble in a variety of polar organic solvents and afforded transparent and relatively flexible to brittle films by solution casting.     

Enzymatic Polyketide Chain Branching To Give Substituted Lactone,Lactam, and Glutarimide Heterocycles

Polyketides typically result from head‐to‐tail condensation of acyl thioesters to produce highly functionalized linear chains. The biosynthesis of the phytotoxin rhizoxin, however, involves a polyketide synthase (PKS) module that introduces a δ‐lactone chain branch through Michael addition of a malonyl extender to an α,β‐unsaturated intermediate unit. To evaluate the scope of the branching module, polyketide mimics were synthesized and their biotransformation by the reconstituted PKS module from the Rhizopus symbiont Burkholderia rhizoxinica was monitored in vitro. The impact of the type and configuration of the δ‐substituents was probed and it was found that amino‐substituted surrogates yield the corresponding lactams. A carboxamide analogue was transformed into a glutarimide unit, which can be found in many natural products. Our findings illuminate the biosynthesis of glutarimide‐bearing polyketides and also demonstrate the utility of this branching module for synthetic biology.     

Synthesis of 2α- and 2β-substituted-14-epi-previtamin D3 and their genomic activity

2α- and 2β-Substituted analogs of 14-epi-previtamin D₃ were synthesized and isolated after thermal isomerization of 14-epi-vitamin D₃ triene at 80 °C. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were tested, and the 2α-methyl-substituted analog was found to have greater genomic activity than 14-epi-previtamin D₃. We found that modification at the C2 position of the seco-steroidal skeleton afforded interesting effects for biological genomic activity for the previtamin D form as well as the natural vitamin D form.     

Development of a new class of (1S,3R,4R)-2-azabicyclo[2.2.1]heptane-oxazoline ligands and their application in asymmetric transfer hydrogenation

New 2-aza-norbornane-oxazoline compounds were synthesized and evaluated as ligands in the transfer hydrogenation of acetophenone. The best catalyst prepared in situ from [IrCl₂(COD)]₂ and a ligand afforded 1-(S)-phenylethanol in good yields and 79% ee.     

The synthesis and biological activity of novel spiro-isoxazoline C-disaccharides based on 1,3-dipolar cycloaddition of exo-glycals and sugar nitrile oxides

A series of novel spiro-isoxazoline C-disaccharides were synthesized by the key step of 1,3-dipolar cycloaddition reactions of exo-glycals and sugar nitrile oxides, and followed by catalytic debenzylation in the presence of Pd(OH)₂/C. The cycloaddition reactions were carried out stereoselectively and afforded α-isomers exclusively except in the case of galactose. The biological activities of the novel disaccharides against the glycosidases (α-amylase, α-glucosidase, and β-glucosidase) and HIV and BVDV were evaluated.     

Synthesis of 2,6-diaryl-1,2-dihydropyridines through a 6π-electrocyclization of N-sulfonylazatrienes

The development of an efficient synthetic method toward substituted 1,2-dihydropyridines from cinnamylideneacetophenones is reported. The key intermediates N-sulfonylazatrienes were synthesized through a TiCl₄-mediated direct condensation of primary sulfonamides with the substituted (E,E)-cinnamylideneacetophenones. The 6π-electrocyclization of these intermediates, catalyzed by a Lewis acid, selectively afforded the desired products in good yields.     

Synthesis of organic–inorganic sorbent containing phenylboronic acid as glucose-binding ligand

A copolymer with N-allylaminophenylboronic acid has been synthesized from a water-soluble N-vinylpyrrolidone–acrolein diethyl acetal copolymer. Immobilization of the obtained copolymer on silica gel afforded an organic–inorganic sorbent capable of sorbing glucose from model solutions.     

Formal synthesis of Abyssomicin C

An alternative strategy towards Abyssomicin C (1) is described. The key ene-diene intermediate is synthesized via a Kishi type coupling of an E/Z mixture of triene-iodide 7 and a suitably functionalized derivative of 2,4-dimethylglutaric acid. A final in situ isomerization/intramolecular Diels-Alder cyclization resulted in the formation of the known intermediate 3 as a single isomer in high yield. Further heating of 3 using excess of iodine, afforded iodo-derivative 23, having the entire carbon skeleton of Abyssomicin D.     

Nitroketene acetal chemistry: efficient synthesis of 2-amino-3-nitro-4H-chromenes

Base-catalyzed reaction of the nitroketene N,S-acetals and the ring substituted 2-hydroxybenzaldehydes afforded a combinatorial library of the 2-alkylamino-3-nitro-4-alkylsulfanyl 4H-chromenes in excellent yields. Nucleophilic displacement of the C4 alkylsulfanyl group with different thiols afforded 4H-chromenes with structural diversity.     

The simple solvent-free synthesis of 1H-quinazoline-2,4-diones using supercritical carbon dioxide and catalytic amount of base

Only supercritical carbon dioxide (scCO₂) as a reactant and a solvent, and catalytic amount of base (DBU (1,8-diazabicyclo[5.4.0]undec-7-ene), DBN (1,5-diazabicyclo[4.3.0]non-5-ene), Dabco^® (1,4-diazabicyclo[2.2.2]octane), and triethylamine) afforded 1H-quinazoline-2,4-diones in good to excellent yields from 2-aminobenzonitriles. 6,7-Dimethoxy-1H-quinazoline-2,4-dione, which is a key intermediate of medicines (Prazosin, Bunazosin, and Doxazosin) was synthesized successfully in a 97% yield, using 0.1 equiv of DBU under scCO₂ (10 MPa) at 80 °C.