Steroid esters of benzophenonecarboxylic acids, benzophenoneacetic acids, and homologs are prepared. Circular dichroism studies indicate that in some of these compounds the benzophenone chromophore can pack on the steroid; these data and phosphorescence lifetime data are interpretable in terms of conformation predicted from molecular models. On irradiation, various of these esters undergo intramolecular attack by the attached benzophenone on the steroid hydrogens. The products can be predicted from molecular models, and considerable control of steroid functionalization can be achieved by appropriate choice of reagent. Controls establish that this photochemistry is directed mainly by the geometry of the ester. Starting with 3a-cholestanol, appropriate esters can direct a photochemical dehydrogenation exclusively into ring D, at the opposite end of the molecule, leading to useful remote functionalization.

BackgroundPersistent vascular inflammation has been implicated as an important cause for a higher prevalence of cardiovascular disease (CVD) in HIV-infected adults. In several populations at high risk for CVD, vascular 18Fluorodeoxyglucose (18FDG) uptake quantified using 3D-positron emission-computed tomography (PET-CT) has been used as a molecular level biomarker for the presence of metabolically active proinflammatory macrophages in rupture-prone early atherosclerotic plaques. We hypothesized that 18FDG PET-CT imaging would detect arterial inflammation and early atherosclerosis in HIV-infected adults with modest CVD risk.MethodsWe studied 9 HIV-infected participants with fully suppressed HIV viremia on antiretroviral therapy (8 men, median age 52 yrs, median BMI 29 kg/m2, median CD4 count 655 cells/μL, 33% current smokers) and 5 HIV-negative participants (4 men, median age 44 yrs, median BMI 25 kg/m2, no current smokers). Mean Framingham Risk Scores were higher for HIV-infected persons (9% vs. 2%, p < 0.01). 18FDG (370 MBq) was administered intravenously. 3D-PET-CT images were obtained 3.5 hrs later. 18FDG uptake into both carotid arteries and the aorta was compared between the two groups.ResultsRight and left carotid 18FDG uptake was greater (P < 0.03) in the HIV group (1.77 ±0.26, 1.33 ±0.09 target to background ratio (TBR)) than the control group (1.05 ± 0.10, 1.03 ± 0.05 TBR). 18FDG uptake in the aorta was greater in HIV (1.50 ±0.16 TBR) vs control group (1.24 ± 0.05 TBR), but did not reach statistical significance (P = 0.18).ConclusionsCarotid artery 18FDG PET-CT imaging detected differences in vascular inflammation and early atherosclerosis between HIV-infected adults with CVD risk factors and healthy HIV-seronegative controls. These findings confirm the utility of this molecular level imaging approach for detecting and quantifying glucose uptake into inflammatory macrophages present in metabolically active, rupture-prone atherosclerotic plaques in HIV infected adults; a population with increased CVD risk.

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[structures: see text] The total syntheses of the amaryllidaceae alkaloids haemanthidine, pretazettine, and tazettine as optically pure enantiomers are reported. Using D-mannose as the starting material, the critical relative stereochemical relationships are established with an intramolecular nitrone-alkene cycloaddition reaction. The synthetic route leads successively to (-)-haemanthidine and then to (+)-pretazettine and (+)-tazettine, taking advantage of the well-established complex relationships among these three alkaloids.