SYNTHESIS OF NEW ANTHRACYCLINE DERIVATIVES CONTAINING PYRUVIC,ASPARTIC, OR N-ACETYLASPARTIC ACID MOLECULE

ABSTRACT

The new anthracycline analogues (2–10) as potential anticancer agents were synthesized from daunomycin (1a) and doxorubicin (1b). Compounds 2, 6, and 7 were prepared by the nucleophilic displacement type esterification of a 14-bromodaunomycin (1c) with a sodium pyruvate, aspartate, and N-acetylaspartic acid, respectively. Whereas compounds (3, 8) and (4, 9) were prepared by the reaction of daunomycin (1a) or doxorubicin (1b) with one equivalent of the corresponding acids in the presence of EDCI/PP, compounds (5, 10) were obtained from 1b by reaction with two equivalents of the corresponding acids in the same manner.     

SYNTHESIS OF NEW OXAMIDE DERIVATIVES OF D-GLUCOSAMINE AND ALIPHATIC OR AROMATIC AMINES

New oxamides, derivatives of D-glucosamine and aliphatic or aromatic amines were prepared by acylation of methyl 3,4,6-tri-O-acetyl-2-acetamido-2-deoxy-α- or -β-D-glucopyranoside (1c or 1d) with oxalyl chloride, followed by reaction with amine. The reaction was assumed to proceed by the intermediate of N-carbomethoxy N-(methyl 3,4,6-tri-O-acetyl-2-deoxy-α or β-D-glucopyranosid-2-yl) oxamic acid chloride which reacted with amines, and afforded N-acetyl, N-(methyl 3,4,6-tri-O-acetyl-2-deoxy-α- or -β-D-glucopyranosid-2-yl), N′-alkyl or aryloxamide (5–7), and N-(methyl 3,4,6-tri-O-acetyl-2-deoxy-α- or -β-D-glucopyranosid-2-yl), N′-alkyl or aryloxamide (8–13).     

PREPARATION AND CHARACTERIZATION OF CLUSTERS CONTAINING THE CoMRuS (M=Mo OR W) CORE

Abstract

The reaction of (μ₃-S)RuCo₂(CO)₉ with functionally substituted cyclopentadienyl tricarbonyl metal anions M(CO)₃(C₅H₄C(O)R) (M = Mo, W; R = OEt, CH₂CH₂COOMe) in THF under reflux gave new chiral skeleton clusters (μ₃-S)RuCoM(CO)₈(C₅H₄C(O)R) [M = Mo, R = OEt (1); M = W, R = OEt (2); M = Mo, R = CH₂CH₂COOMe (3); M = W, R = CH₂CH₂COOMe (4)]. These complexes were characterized by elemental analysis, IR and ¹H NMR spectra. The molecular structure of compound (1) was determined by single-crystal X-ray diffraction methods.     

Synthetic Studies on Sialoglycoconjugates 88: Synthesis of Ganglioside GM3 and GM4 Analogs Containing 2- OR 3-Branched Fatty-Alkyl Residues in Place of Ceramide

ABSTRACT

Each of four ganglioside GM₄ and GM₃ analogues containing 2- or 3-branched fatty alkyl residues in place of ceramide have been synthesized. Coupling of O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→3)-2,4,6-tri-O-benzoyl-α-D-galactopyranosyl trichloroacetimidate (13) or O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-glacto-2-nonulopyranosylonate)-(2→3)-O-(2,4-di-O-acetyl-6-O-benzoyl-β-D-galactopyranosyl)-(1→4)-3-O-acetyl-2,4-di-O-benzoyl-α-D-glucopyranosyl trichloroacetimidate (14) with 2- or 3-branched fatty-alkyl-1-ols (9-12), prepared from the corresponding branched fatty acids by methyl esterification and reduction, using BF₃Ot₂ gave the corresponding ganglioside analogues (15, 17, 19, 21, 23, 25, 27, 29) in good yields, which were coverted, via O-deacylation and de-esterification, into the title compounds.     

SELECTIVE ALKYLATION/ACYLATION OF DI- OR TRIANIONS: EXPEDITIOUS DERIVATIZATION OF ENDOTHELIN ANTAGONISTS[1]

ABSTRACT

Sitaxsentan sodium (1, TBC11251Na) is an ET_A selective endothelin antagonist under clinical development for pulmonary arterial hypertension and congestive heart failure. Second generation compounds, as exemplified by TBC2576 (2) are currently under development in our laboratories. To rapidly access analogs of 1 and 2, a route was developed for the selective alkylation or acylation of the corresponding di- or trianions derived from these two highly functionalized compounds. We report here on this straightforward, yet effective, procedure consisting of treating the di- or trianions with an excess amount of electrophiles, followed by a rapid quench. In this manner, selective alkylation or acylation of 1 and 2 was achieved with satisfactory yields.     

FACILE SYNTHESIS OF POLYSUBSTITUTED CYCLOPENTENYLAMINES OR γ-HYDROXYAMIDES BY SAMARIUM DIIODIDE

ABSTRACT

Promoted by SmI₂, γ-Hydroxyamides or polysubstituted cyclopentenylamines were synthesized from 1,1-diaryl-2,2-dicyanoethylenes or diaryl ketones and cinnamoyl amides under mild conditions in good yields.     

PREPARATION AND CHARACTERIZATION OF CLUSTER COMPLEXES CONTAINING ONE OR TWO C2M2 (M = Co,Mo) CORES

Abstract

The reaction of dipropargylether with Mo₂(C₅H₄R)₂(CO)₄ (R = H, COOCH₂CH₃), prepared by refiuxing a toluene solution of Mo₂(C₅H₄R)₂(CO)₆ (R = H, COOCH₂CH₃), gave dinuclear cluster complexes (HC₂CH₂OCH₂C₂H-μ)[Mo₂(C₅H₄R)₂(CO)₄] [(1): R = H, (2): R = COOCH₂-CH₃] and tetranuclear cluster complexes [Mo₂(C₅H₄R)₂(CO)₄](μ-HC₂CH₂OCH₂C₂H-μ) [Mo₂(C₅H₄R)₂(CO)₄] [(3): R = H, (4): R = COOCH₂CH₃], respectively. When (1) or (2) was treated with an equimolar amount of octacarbonyldicobalt, the new novel tetranuclear cluster complexes [Co₂CO)₆](μ-HC₂CH₂OCH₂C₂H-μ)(Mo₂(C₅H₄R)₂(CO)₄] [(5): R = H, (6): R = COOCH₂CH₃] were obtained. These complexes were characterized by elemental analysis, IR and ¹H NMR spectra. The molecular structure of complex (3 1/2CH₂C1₂) was determined by single-crystal X-ray diffraction methods.     

SYNTHESIS OF ARYL(OR BENZYL)- (Z)-N-[2-AMINO-1,2-DICYANOVINYL]FORMAMIDINES

ABSTRACT

Starting from readily available ethyl(Z)-N-(2-amino-1,2-dicyanovinyl)formimidate (1), the N-aryl (or benzyl)-N′(-(2-amino-1,2-dicyanovinyl)formamidines (2) can be prepared in good yields by reaction with aromatic amines at room temperature in the presence of a catalytic amount of aniline hydrochloride.     

COMPLEXES OF 1,8-NAPHTHYRIDINES IX. GROUP VIb METAL CARBONYL COMPLEXES CONTAINING 1,8-NAPHTHYRIDINE, 2-METHYL-1,8-NAPHTHYRIDINE OR trans-DECAHYDRO-1,8-NAPHTHYRIDINE

Abstract

Complexes of the type M(CO)₅(N-N), M(CO)₄(N-N) and M(CO)₃(N-N)₂, where M is Cr, Mo or W and N-N is 1,8-naphthyridine(napy), 2-methyl-1,8-naphthyridine(2-mnapy) or trans-decahydro-1,8-naphthyridine(dhnapy), have been prepared and characterized by infrared and proton magnetic spectroscopy. Complexes of the type Mo(CO)₃(N-N)(napy), where N-N is 1,10-phenanthroline(phen), 2,2′-bipyridine(bipy), 2,9-dimethyl-1,10-phenanthroline(2,9-dmphen) or 2,7-dimethyl-1,8-naphthyridine (2,7-dmnapy), were also prepared and characterized by infrared spectroscopy. In these systems, the various naphthyridine donors exhibit the unique ability to behave as both mono- and bidentate ligands. The mode of bonding between the metal and heterocycles is determined by proton magnetic resonance data.     

SYNTHESIS AND BIOLOGICAL ACTIVITIES OF NEW INDOLE DERIVATIVES CONTAINING SULFIDE AND/OR SULFONE MOIETIES. PART I

Abstract

4-Amino-halonitrodiphenyl sulfides(I) and/or 4-amino-halonitrodiphenyl sulfones have been found to react with isatin, N-acetyl isatin, isatin-N-Mannich bases, indole-3-carboxaldehyde and N-substituted indole-3-carboxaldehyde producing the corresponding indole derivatives. The biological activity of some of these products was screened against selected strains of bacteria.     

CONFORMATIONS OF 4,5,6-TRIPHENYL-TETRAHYDRO-1,3-THIAZINE-2-THIONES AND THEIR N-ALKYL DERIVATIVES. UNUSUAL THIAZINETHIONE OR AZETIDINE FORMATION UPON REACTION OF 3-AMINO- AND 3-METHYLAMINO-1,2,3-TRIPHENYLPROPYL CHLORIDES WITH POTASSIUM ETHYLXANTHATE

Abstract

Reaction of 3-amino- or 3-methylamino-1,2,3-triphenylpropyl chlorides (6 or 7) with potassium ethylxanthate leads to 4.5.6-triphenyl-tetrahydro-,3-thiazine-2-thione 1 or 1-methyl-2,3,4-triphenylazetidine 8 depending on the N-substitution. Conformational distribution of all possible diastereoisomeric thiazinethiones 1 and their N-alkyl derivatives 2–5 is determined by means of ¹H NMR spectroscopy. Allylic strain caused by N- substituents in the trans,cis-isomers strongly shifts the equilibrium between conformations with a,a,e or e,e,a phenyl groups towards the conformer with an axial neighbouring Ph-4 group. Vicinal couplings data for the diastereoisomeric azetidine 8 show different ring geometry depending on the configuration.     

Pt(II) ASSISTED DEOXYGENATION OF COORDINATED SULFOXIDES BY HYDROCHLORIC- OR HYDROBROMIC ACID

Abstract

The interaction of the complexes (Et₄ N)[Pt(R₂ SO)X₃] (R = Me, Et, CH₂ Ph, X [dbnd] C1; R [dbnd] Me, X [dbnd] Br) and cis-[Pt(Me₂ SO)₂ Cl₂] with concentrated HX (X [dbnd] Cl. Br) results in the reduction of the coordinated sulfoxides and oxidation of Pt(II) to Pt(IV). As a result [Pt(R₂ S)X₅ and [Pt(R₂S)₂ X₄] are formed. Ligands R₂ S can be removed from the complexes and isolated in a free state.     

HYDROXY AND/OR CARBOXY SUBSTITUTED PHOSPHONIC AND BISPHOSPHONIC ACIDS USABLE AS CORROSION AND SCALE INHIBITORS

Abstract

2-Dihydroxyphosphonyl-2-hydroxy-propionic acid (DHHPA), 1,4-bis[(dihydroxyphosphonyl)hydroxy-methyl]benzene (BDHB) and 2,3-bis(dihydroxyphosphonyl)-1,4-butanedioic acid (BDBA) were synthesized by acid catalyzed hydrolysis of the corresponding substituted phosphonates or bisphosphonates. The structure of these compounds was confirmed by elemental analysis as well as by infrared (IR) and proton nuclear magnetic resonance (¹H-NMR) spectroscopy. They can be used as corrosion and scale inhibitors.     

TISSUE SELENIUM LEVELS AND GROWTH RESPONSES OF MICE FED SELENOMETHIONINE,SE-METHYLSELENOCYSTEINE OR SODIUM SELENITE

Abstract

Mice fed diets containing selenomethionine at a level of 20 ppm selenium and raised to 30 ppm selenium at 3 weeks on experiment showed (1) delayed response to selenium toxicity, (2) slow recovery from the toxicity after removal of selenium from the diet and (3) relatively high deposition and retention of tissue selenium. These data suggest that selenomethonine initially becomes incorporated in to the primary structure of proteins and as such is not particularly toxic. However, upon its slow removal from protein, selenomethionine becomes toxic by forming selenium IV compounds through a pathway similar to that followed by methionine.

Mice fed diets containing sodium selenite or Se-methylselenocysteine at the same level of selenium as the selenomethionine diet showed (1) immediate response to selenium toxicity (2) rapid recovery from the toxicity after removal of selenium from the diet and (3) relatively low deposition and relatively rapid depletion of tissue selenium. These data suggest that sodium selenite and Se-methylselenocysteine ultimately follow similar metabolic pathways and do not become part of the primary structure of proteins. A possible metabolic route for Se-methylselenocysteine is that it is oxidized to toxic selenium IV compounds through an oxidative pathway similar to that followed by S-methylcysteine.     

NOVEL SYNTHESIS OF THIOL ESTERS VIA A SULFUR TRANSFER AGENT-POTASSIUM ALKYL OR BENZYL DITHIOCARBONATES

Abstract

The reaction of certain acid chlorides with potassium alkyl or benzyl dithiocarbonates afforded a novel synthesis of thiol esters.     

NEW DERIVATIVES OF 4,5-BENZO-1,3,2-OXAZA (OR D1AZA)-PHOSPHOLANE FROM CONVENIENT CONDENSATION OF SUBSTITUTED UREA WITH TRIS(DIALKYLAMINO)PHOSPHINE

Abstract

The condensation of N-phenyl-N′-(2-hydroxylphenyl)urea or N-phenyl-N′-(2-aminophenyl)urea with tris(dia1kylamino)phosphine afforded derivatives of 4,5-benzo-1,3,2-oxaza (or diaza)-phospholane which formed intramolecular hydrogen bond. The cleavage of the amide bond to give N,N-dialky1-N′-phenylurea together with polymers of 1,3,2-benzodiazaphosphole was observed in the latter reaction.     

Use of Tetrahydro-2H-1,3-Oxazinones as Aminopropylation Agents

Treatment of tetrahydro-2H-1,3-oxazin-2-one (1) or the 3-methyl derivative 2 with aniline salts or thiophenols at 180 °C affords the corresponding N-aryl-1,3-propanediamines 3 or 3-(arylthio)propanamines 4 in good yields.     

STRUCTURES AND PROPERTIES OF COPPER(II) COMPLEXES WITH IMINODIACETATO AND IMIDAZOLE OR RELATED LIGANDS. I. CRYSTAL STRUCTURE OF AQUA(IMIDAZOLE) (IMINODIACETATO)COPPER(II) MONOHYDRATE AND (IMIDAZOLE)(N-CARBOXYMETHYL-D,L-THREONINATO)COPPER(II)

Abstract

The crystal structures of two mixed-ligand copper(II) complexes having iminodiacetate(2-) (IDA) or N-carboxymethyl-D,L-threoninato(2-) ion (CMT) as terdentate ligands and imidazole (ImH) as an N-heterocyclic ligand are reported. Both compounds crystallize in the orthorhombic system, space group Pbca with Z = 8. Aqua(imidazole)(iminodiacetato)copper(II) monohydrate (I,R = 0.065, R _w = 0.075) consists of H₂O molecules and [Cu(IDA)(ImH)(H₂O)] complex units in a hydrogen bonding network. The structure of imidazole(N-carboxymethyl)-D,L-threoninatocopper(II) (IV, R = 0.066, Rω 0.078) is built up of hydrogen bonded polynuclear chains. In both compounds the Cu(II) ion exhibits a flattened and distorted square-based pyramidal coordination, with a terdentate aminoacidate ion, IDA or CMT, and one ImH ligand at the base and H₂O (in I) or the oxygen atom of the OH side chain from one adjacent CMT ion (in IV) as the fifth apical ligand. The nearly coplanar conformation of the two five-membered chelate rings in I and IV is discussed in connection with the known structure of corresponding aquacomplexes (with H₂O instead of ImH) and the ability of terdentate aminoacids to give ternary Cu(II) complexes having two N-heterocyclic donors (2 ImH or one 2,2′-bipy) per Cu(II) atom.     

Lanthanide triiodide-catalyzed amination of phthalonitrile. The structure of 1-isopropylamino-3-(isopropylimino)isoindole

The reactions of phthalonitrile with MeNH₂, PrⁿNH₂, and PrⁱNH₂ in the presence of catalytic amounts of LnI₃ (Ln = Nd or Dy) or LnI₃(THF)₃ (Ln = Gd or Nd) afford 1,3-bis(alkylimino)isoindolines (Alk = Me (1), Prⁿ (2), or Prⁱ (3), respectively). Under analogous conditions, 2-aminopyridine gives 1,3-bis(2-pyridylimino)isoindoline (4). The X-ray diffraction study of compound 3 showed that, in the crystalline state, this compound exists as the isomer, 1-isopropylamino-3-(isopropylimino)isoindole.