Biomedical subjects

David W Porter

Publications and source records attributed to David W Porter.

6 recordsLinked to original sources

PubMed2006

Formation of surface-bound acyl groups by reaction of acyl halides on ge(100)-2x1.

We have investigated the reaction of a series of acyl halides, including acetyl chloride, acetyl bromide, acetyl-d3 chloride, benzoyl chloride, and pivaloyl chloride, on Ge(100)-2x1 with multiple internal reflection infrared (MIR-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS), and density functional theory (DFT). Infrared spectra following saturation exposures of acetyl chloride and acetyl bromide to Ge(100)-2x1 at 310 K are nearly identical, both exhibiting strong nu(C=O) stretching peaks near 1685 cm-1 and no vibrational modes in the nu(Ge-H) region. These data provide strong evidence for the presence of a surface-bound acetyl group on Ge(100)-2x1, which results from a C-X dissociation reaction (where X=Cl, Br). For acetyl chloride, DFT calculations predict that the barrier to C-Cl dissociation is only 1 kcal/mol above a chlorine-bound precursor state and is considerably smaller than barriers leading to the [2+2] C=O cycloaddition and alpha-CH dissociation products. In addition to the C-X dissociation product, both infrared and photoelectron results point to the presence of a second structure for acetyl halides where the oxygen of the surface-bound acetyl group donates charge to a nearby surface atom. This interaction is not observed for benzoyl chloride and pivaloyl chloride.

Acylation↗

PubMed2004

Rhodanine-3-acetic acid derivatives as inhibitors of fungal protein mannosyl transferase 1 (PMT1).

The first inhibitors of fungal protein: mannosyl transferase 1 (PMT1) are described. They are based upon rhodanine-3-acetic acid and several compounds have been identified, for example, 5-[[3-(1-phenylethoxy)-4-(2-phenylethoxy)phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidineacetic acid (5a), which inhibit Candida albicans PMT1 with IC(50)s in the range 0.2-0.5 microM. Members of the series are effective in inducing changes in morphology of C. albicans in vitro that have previously been associated with loss of the transferase activity. These compounds could serve as useful tools for studying the effects of protein O-mannosylation and its relevance in the search for novel antifungal agents.

Candida albicans↗

PubMed2004

Concise asymmetric synthesis of (-)-sparteine.

A six-step asymmetric synthesis of natural (-)-sparteine from ethyl 7-iodohept-2-enoate is reported, involving a connective Michael addition of an amino ester-derived enolate to an alpha,beta-unsaturated amino ester.

Amino Acids↗

PubMed2004

2,3-Dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acid derivatives: a novel class of small molecule heparanase inhibitors.

A novel class of 2,3-dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acids are described as inhibitors of the endo-beta-glucuronidase heparanase. Several of the compounds, for example, 2-[4-propylamino-5-[5-(4-chloro)phenyl-benzoxazol-2-yl]phenyl]-2,3-dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acid (9c), display potent heparanase inhibitory activity (IC(50) 200-500 nM) and have high selectivity (>100-fold) over human beta-glucuronidase. They also show anti-angiogenic effects. Such compounds should serve as useful biological tools and may provide a basis for the design of novel therapeutic agents.

Carboxylic Acids↗

PubMed2004

Histiocytic sarcoma with interdigitating dendritic cell differentiation.

The authors describe a rare tumor with overlapping features of true histiocytic sarcoma and interdigitating dendritic cell sarcoma occurring in infancy. A 3-month-old boy presented with hepatosplenomegaly and abdominal distention. He presented a diagnostic challenge at initial presentation despite extensive investigations. On follow-up at age 16 months he had progressive splenomegaly, thrombocytopenia, and worsening coagulopathy. A diagnosis of histiocytic sarcoma with interdigitating dendritic cell differentiation was established after an open biopsy of liver and spleen. A repeat liver biopsy coupled with splenic biopsy is recommended in young children with unexplained hepatosplenomegaly and thrombocytopenia.

Biopsy↗

PubMed2003

Synthesis of sparteine-like chiral diamines and evaluation in the enantioselective lithiation-substitution of N-(tert-butoxycarbonyl)pyrrolidine.

Three chiral diamines were synthesised and evaluated as sparteine surrogates in the lithiation-substitution of N-(tert-butoxycarbonyl)pyrrolidine. The synthesis and attempted resolution of sparteine-like diamines [(1S*,2R*,8R*)-10-methyl-6,10-diazatricyclo[6.3.1.0(2,6)]dodecane and (1S*,2R*,9R*)-11-methyl-7,11-diazatricyclo[7.3.1.0(2,7)]tridecane] (via inclusion complex formation) are reported. Unfortunately, it was only possible to resolve the diazatricyclo[7.3.1.0(2,7)]tridecane compound. An alternative route to (1R,2S,9S)-11-methyl-7,11-diazatricyclo[7.3.1.0(2,7)]tridecane starting from the natural product, (-)-cytisine, is described. This simple three-step route furnished gram-quantities of a (+)-sparteine surrogate. X-Ray crystallography of an intermediate in the route, (1R,5S,12S)-3-methoxycarbonyldecahydro-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one, enabled the stereochemistry of all of the tricyclic diamines described in this paper to be unequivocally established. Two other diamines, starting from (S)-proline and resolved 2-piperidine ethanol, were prepared using standard methods. These diamines lacked the bispidine framework of (-)-sparteine and were found to impart vastly inferior enantioselectivity. It was concluded that, for the asymmetric lithiation substitution of N-Boc pyrrolidine, a rigid bispidine framework and only three of the four rings of (-)-sparteine are needed for high enantioselectivity. Furthermore, it is shown that diamine (1R,2S,9S)-11-methyl-7,11-diazatricyclo[7.3.1.0(2,7)]tridecane is the first successful (+)-sparteine surrogate.

Journal Article↗