Biomedical subjects

R Hazell

Publications and source records attributed to R Hazell.

3 recordsLinked to original sources

PubMed2000

Synthesis of the benzophenone fragment of balanol via an intramolecular cyclization event.

Studies are reported on the use of either a 7-exo radical cyclization or an intramolecular Heck reaction as the key step for the construction of the benzophenone fragment of the PKC inhibitor, balanol. Whereas, the former approach was unsuccessful, the Heck reaction proved to be viable for the coupling of two fully functionalized aryl subunits affording regioselectively a biaryl seven-membered lactone with an exocyclic alkene as the major component, in contrast to the competing eight-membered ring lactone. Hydrolysis of the lactone followed by oxidative cleavage of the alkene with ruthenium tetraoxide completed this short synthesis of the benzophenone unit.

Azepines↗

PubMed2000

Studies on the SmI2-promoted pinacol-type cyclization: synthesis of the hexahydroazepine ring of balanol

The efficiency of the samarium(II) iodide induced pinacol-type coupling for the construction of seven-membered cyclic amino alcohols has been investigated. With the acyclic carbonylhydrazones 6 and 16, good yields of the hexahydroazepines 22 and 23 were obtained (56-57%) with high trans-selectivity (= 10:1), which compares well with similar reactions generating the corresponding five- and six-membered carbocycles (Fallis, A. G.; Sturino, C. F. J. Am. Chem. Soc. 1994, 116, 7447). It is essential for ring formation that the strongly electron-donating ligand, hexamethylphosphoramide, be present, as in its absense intermolecular pinacol coupling forming the diols 27-30 is the dominant reaction. Hence, the role for HMPA appears not only to increase the rate of electron transfer but also to modulate rate constants for the subsequent reactions (cyclization and pinacol coupling) of the intermediate ketyl. This ring forming reaction has been applied to the construction of the fully functionalized hexahydroazepine ring of the PKC inhibitor, balanol. Initial attempts to develop an asymmetric version of this reaction indicate the use of chiral ligands based on the structure of HMPA.

Journal Article↗

PubMed1998

Devolution. Separate ways.

Devolution will bring health policy under the democratic control of the directly elected Scottish parliament and Welsh assembly. Some fear that members of these bodies may wish to interfere in service delivery, rather than concentrating on strategy. Devolution could highlight anomalies in health spending. Many professionals fear that devolution will fragment UK-wide policy networks.

Budgets↗