Efficacious N-protection of O-aryl sulfamates with 2,4-dimethoxybenzyl groups

Sulfamates are important functional groups in certain areas of current medicinal chemistry and drug development. Alcohols and phenols are generally converted into the corresponding primary sulfamates (ROSO(2)NH(2) and ArOSO(2)NH(2), respectively) by reaction with sulfamoyl chloride (H(2)NSO(2)Cl). The lability of the O-sulfamate group, especially to basic conditions, usually restricts this method to a later stage of a synthesis. To enable a more flexible approach to the synthesis of phenolic O-sulfamates, a protecting group strategy for sulfamates has been developed. Both sulfamate NH protons were replaced with either 4-methoxybenzyl or 2,4-dimethoxybenzyl. These N-protected sulfamates were stable to oxidising and reducing agents, as well as bases and nucleophiles, thus rendering such masked sulfamates suitable for multi-step synthesis. The protected sulfamates were synthesised by microwave heating of 1,1'-sulfonylbis(2-methyl-1H-imidazole) with a substituted phenol to give an aryl 2-methyl-1H-imidazole-1-sulfonate. This imidazole-sulfonate was N-methylated by reaction with trimethyloxonium tetrafluoroborate, which enabled subsequent displacement of 1,2-dimethylimidazole by a dibenzylamine (e.g. bis-2,4-dimethoxybenzylamine). The resulting N-diprotected, ring-substituted phenol O-sulfamates were further manipulated through reactions at the aryl substituent and finally deprotected with trifluoroacetic acid to afford a phenol O-sulfamate. The use of 2,4-dimethoxybenzyl was particularly attractive because deprotection occurred quantitatively within 2 h at room temperature with 10% trifluoroacetic acid in dichloromethane. The four key steps in the protocol described [reaction of 1,1'-sulfonylbis(2-methyl-1H-imidazole) with a phenol, methylation, displacement with a dibenzylamine and deprotection] all proceeded in very high yields.     

Searching for cyclin-dependent kinase inhibitors using a new variant of the cope elimination

beta-Piperidinoethylsulfides are oxidized by m-chloroperbenzoic acid to intermediates containing both N-oxide and sulfone functions. These undergo a Cope-type elimination to a vinylsulfone that can be captured by amines to afford beta-aminoethylsulfones. When a beta-aminoethylsulfone group is linked to the 4-position of a phenyl group attached at N-2 of O6-cyclohexylmethylguanine, the resulting derivatives are inhibitors of the cyclin-dependent kinase CDK2. One of the most potent inhibitors (IC50 = 45 nM) contained a N-3-hydroxypropyl group on the aminoethylsulfonyl substituent. The crystal structure of this inhibitor bound to CDK2/cyclin A was determined and shows an unusual network of hydrogen bonds. The synthetic methodology developed can be utilized in multiple-parallel format and has numerous potential applications in medicinal chemistry.     

Magnetoconductivity tensor analysis of anomalous transport effects in neutron irradiated HgCdTe epilayers

Hg_1−xCd_xTe(x0.22) samples grown by LPE on CdZnTe(111B)-oriented substrates were exposed to various doses of thermal neutrons (1.0×10¹⁶−1.7×10¹⁶ n/cm²) and subsequently annealed for 24 h in Hg overpressure to remove damage and reduce the presence of Hg vacancies. Extensive magnetotransport measurements were performed on these samples as part of an investigation into the use of elemental transmutation for efficient p-type doping of this material. The data were analyzed using a multi-carrier approach which incorporates various scattering mechanisms and the presence of two conduction channels of differing alloy content to describe the changes in the transport properties due to neutron irradiation.     

Symmetry coupling coefficients for the double groups C n*, D n* and T*

By coupling linear combinations of the |JM ket vectors which transform as irreducible representations of C_n *, D_n * and T*, symmetry coupling coefficients for these groups are calculated. Also, ? coefficients as defined by Golding [1] are evaluated.     

A study of the effect of non-collinear Zeeman,hyperfine and fine structure tensors on E.S.R. spectra

Second order perturbation solutions are given to the general experimental hamiltonian :

where the axes of the g, D and A tensors may be non-collinear. The effects of the non-collinearities are discussed in terms of the modifications of the E.S.R. parameters for both single crystal and polycrystalline samples. The principles are illustrated for the E.S.R. of the formyl radical from published single crystal and powder data.