Access to 2-Fluorinated Aziridine-2-phosphonates from ,-Halofluorinated -Iminophosphonates-Spectroscopic and Theoretical Studies.

The efficient one-pot halofluorination of a -enaminophosphonate/-iminophosphonate tautomeric mixture resulting in ,-halofluorinated -iminophosphonates is reported. Subsequent imine reduction gave the corresponding -aminophosphonates as a racemic mixture or with high diastereoselectivity. The proposed protocol is the first example of a synthesis of -inactivated aziridines substituted by a fluorine and phosphonate moiety on the same carbon atom.

Highly Diastereoselective Construction of Carbon- Heteroatom Quaternary Stereogenic Centers in the Synthesis of Analogs of Bioactive Compounds: From Monofluorinated Epoxyalkylphosphonates to α-Fluoro-, β-, or γ-Amino Alcohol Derivatives of Alkylphosphonates.

The synthesis of the stable surrogates of an important amino acid ()-4-amino-3-hydroxybutyric acid (GABOB) such as substituted hydroxy aminophosphonic acids bearing a quaternary stereogenic center is presented. Highly diastereoselective formations of fluorinated spiroepoxy alkylphosphonate or related tertiary carbon-containing oxiranes from β-keto phosphonates possessing methyl, phenyl, or cyclohexenyl substituents, are reported. Stereoselective acid-promoted epoxide opening by bromide or azide followed by reduction/protection afforded tertiary bromides or -Boc derivatives of β-amino-γ-hydroxy alkylphosphonates in most cases, while the reactions of oxiranes with different amines yielded their β-hydroxy-γ-amino regioisomers.

Pyrrolidine and oxazolidine ring transformations in proline and serine derivatives of α-hydroxyphosphonates induced by deoxyfluorinating reagents.

Transformations of α-hydroxyphosphonates derived from proline or serine by treatment with different deoxyfluorinating reagents (DAST, Deoxofluor, PyFluor) are reported. Depending on the applied reagent, as well as the protecting group used (-Cbz, -Boc, -Bn) different types of products are observed. The reaction of -Cbz or -Boc prolinols with DAST or Deoxofluor due to aziridinium intermediate participation gave fluorinated amino phosphonates such as piperidine and pyrrolidine derivatives and/or oxazolidine-2-ones.

Functionalization of α-hydroxyphosphonates as a convenient route to -tosyl-α-aminophosphonates.

Direct conversion of the α-hydroxyl group by -toluenesulfonamide to yield α-(-tosyl)aminophosphonates is reported. α-Aminophosphonates 23a,b-37a,b were obtained from the corresponding α-hydroxyphosphonates 6a,b-21a,b in the presence of KCO, the retro-Abramov reaction of the appropriate aldehydes, 1-5. The subsequent formation of imines with simultaneous addition of diethyl phosphite provided access to the α-sulfonamide phosphonates 23a,b-37a,b with better diastereoselectivity than in the case of the Pudovik reaction.

AdoHcy hydrolase of Trichomonas vaginalis: studies of the effects of 5'-modified adenosine analogues and related 6-N-cyclopropyl derivatives.

Trypanosoma brucei and Trichomonas vaginalis are both parasitic protozoans that are known to share many similar biochemical pathways. Aristeromycin, as well as 5'-iodovinyl and 5'-oxime analogues of adenosine, are potent inhibitors of AdoHcy hydrolase in T. brucei, an enzyme that catalyses the hydrolysis of AdoHcy to adenosine and L-homocysteine.

Reactions of Trimethylsilyl Fluorosulfonyldifluoroacetate with Purine and Pyrimidine Nucleosides.

Difluorocarbene, generated from trimethylsilyl fluorosulfonyldifluoroacetate (TFDA), reacts with the uridine and adenosine substrates preferentially at the enolizable amide moiety of the uracil ring and the 6-amino group of the purine ring. 2',3'-Di-O-acetyl-3'-deoxy-3'-methyleneuridine reacts with TFDA to produce 4-O-difluoromethyl product derived from an insertion of difluorocarbene into the 4-hydroxyl group of the enolizable uracil ring. Reaction of the difluorocarbene with the adenosine substrates having the unprotected 6-amino group in the purine ring produced the 6-N-difluoromethyl derivative, while reaction with 6-N-benzoyl protected adenosine analogues gave the difluoromethyl ether product derived from the insertion of difluorocarbene into the enol form of the 6-benzamido group.

Vinyl Tris(trimethylsilyl)silanes: Substrates for Hiyama Coupling.

The oxidative treatment of vinyl tris(trimethylsilyl)silanes with hydrogen peroxide in aqueous sodium hydroxide in tetrahydrofuran generates reactive silanol or siloxane species that undergo Pd-catalyzed cross-couplings with aryl, heterocyclic and alkenyl halides in the presence of Pd(PPh(3))(4) and tetrabutylammonium fluoride. Hydrogen peroxide and base are necessary for the coupling to occur while activation of the silanes with fluoride is not required. The conjugated and unconjugated tris(trimethylsilyl)silanes serve as good cross-coupling substrates.

Isolation and characterization of an anticancer catechol compound from Semecarpus anacardium.

Ethnopharmacological Relevance: The fruits and seeds of Semecarpus anacardium are used widely for the treatment of human cancers and other diseases in the Ayurvedic and Sidda systems of medicine in India.

Aim Of The Study: The principal aim of this investigation was to isolate and characterize the anticancer compound from the kernel of Semecarpus anacardium nut.

Materials And Methods: The bioactivity-tailored isolation and detailed chemical characterization were used to identify the active compound.

An unexpected reaction of trimethylsilyl fluorosulfonyldifluoroacetate (TFDA) with imidazoles. Formation of N-difluoromethylthioureas.

A new reaction of the efficient difluorocarbene-generating reagent trimethylsilyl fluorosulfonyldifluoroacetate (TFDA) is reported in which molecules containing an N-alkylimidazole or benzimidazole structure undergo an unexpected one-pot conversion to N-difluoromethylthioureas. [reaction: see text].

Antitrypanosomal activity of 5'-deoxy-5'-(iodomethylene)adenosine and related 6-N-cyclopropyladenosine analogues.

Treatment of the 6-N-cyclopropyl-2',3'-di-O-isopropylideneadenosine 5'-aldehyde with sulfone-stabilized phosphonate or fluorophosphonate reagents followed by stannyldesulfonylations and subsequent iodo- or protiodestannylation gave 6-N-cyclopropyl-5'-deoxy-5'-(iodomethylene)adenosine 8b or its 5'-fluoromethylene analogue 11. Treatment of the 5'-aldehyde with hydroxylamine or dibromomethylene- or cyanomethylene-stabilized Wittig reagents and deprotections gave the oxime 4b, 5'-cyanomethylene 5b, and 5'-dibromomethylene 13b analogues. Dehydrobromination of 13b gave acetylenic compound 14b.