S.W. Baldwin

Asymmetric synthesis with chiral hydroxylamines.: Synthesis of optically pure 4-substituted azetidinones

Abstract The reaction between β-substituted acrylate esters and α-methylbenzyl hydroxyl amine affords diastereoisomeric 5-isoxazolidinones, convenient precursors of simple optically pure 2-azetidinones.

9:30—9:45: Preliminary Evaluation of F-18 Fluorocholine (FCH) as a PET Tumor Imaging Agent

The purpose of this study was to develop and evaluate an F-18 labeled choline tumor imaging agent.FCH was synthesized through the intermediate F-18 fluorobromomethane that was used to alkylate dimethylethanolamine. The isolated FCH was evaluated in PC-3 human prostate cancer cells, PC-3 human prostate cancer xenograft studies, and human prostate and brain tumor patients.FCH was accumulated at a slightly lower rate than FDG in the cultures of PC-3 cells. Inhibition of choline transport and phosphorylation by hemicholinium-3 resulted in a 90% decrease in FCH uptake without altering FDG uptake. FCH had a similar biodistribution as C-14 choline in mice, with the liver and kidneys being the primary sites of uptake. Tumor uptake of FCH and FDG were comparable at 45-60 mins after injections. The tumor:blood ratio was higher for FCH (5.3 +/- 2.4) than for FDG (3.2 +/- 0.3). Brain uptake of FCH was 10% that of FDG. FCH-PET studies were compared to FDG-PET studies. In the prostate cancer patients, more lesions have been seen on the FCH studies than on the FDG studies, and the standardized uptake values (SUV) have been higher with the FCH. Decreases in FCH-PET SUV have been noted in patients treated by androgen deprivation. Patients with suspected recurrent brain tumors have had more clearly defined abnormal accumulation on the FCH-PET scans than on the FDG-PET scans. The FCH is not accumulated by normal cortex.FCH is a promising imaging agent for the evaluation of metastatic prostate cancer and recurrent brain tumor.

Preliminary evaluation of F-18 fluorocholine (FCH) as a PET tumor imaging agent

The purpose of this study was to develop and evaluate an F-18 labeled choline tumor imaging agent.FCH was synthesized through the intermediate F-18 fluorobromomethane that was used to alkylate dimethylethanolamine. The isolated FCH was evaluated in PC-3 human prostate cancer cells, PC-3 human prostate cancer xenograft studies, and human prostate and brain tumor patients.FCH was accumulated at a slightly lower rate than FDG in the cultures of PC-3 cells. Inhibition of choline transport and phosphorylation by hemicholinium-3 resulted in a 90% decrease in FCH uptake without altering FDG uptake. FCH had a similar biodistribution as C-14 choline in mice, with the liver and kidneys being the primary sites of uptake. Tumor uptake of FCH and FDG were comparable at 45-60 mins after injections. The tumor:blood ratio was higher for FCH (5.3 +/- 2.4) than for FDG (3.2 +/- 0.3). Brain uptake of FCH was 10% that of FDG. FCH-PET studies were compared to FDG-PET studies. In the prostate cancer patients, more lesions have been seen on the FCH studies than on the FDG studies, and the standardized uptake values (SUV) have been higher with the FCH. Decreases in FCH-PET SUV have been noted in patients treated by androgen deprivation. Patients with suspected recurrent brain tumors have had more clearly defined abnormal accumulation on the FCH-PET scans than on the FDG-PET scans. The FCH is not accumulated by normal cortex.FCH is a promising imaging agent for the evaluation of metastatic prostate cancer and recurrent brain tumor.

Enantioselective syntheses of homophenylalanine derivatives via nitrone 1,3-dipolar cycloaddition reactions with styrenes

Abstract A new two-step route to derivatives of homophenylalanine is presented. Cycloaddition of a cyclic nitrone glycine template with various styrene derivatives affords good yields of 5-substituted cycloadducts. One-step hydrogenolysis (three bonds) then affords the optically pure α-amino acids related to homophenylalanine.

Diastereoselective diels-alder reactions between substituted 1,3-butadienes and n-α-methylbenzylmaleimide

Abstract The TiCl 4 catalyzed reaction between 2- t -butyl-1,3-butadiene and N-α-methylbenzylmaleimide at −65°C affords diastereomeric Diels-Alder adducts in a 15:1 ratio. The structure of the major adduct was determined by x-ray.

Preparation and evaluation of a cyclic acyl nitrone as a synthon for stereospecific α-amino acid synthesis

Abstract The preparation and characterization of cyclic optically active (5R)-3,4,5,6-tetrahydro-5-phenyl-2H-1,4-oxazin-2-one-N-oxide (2) is described. This nitrone, which is viewed as a template for the synthesis of γ-oxygenated α-amino acids, reacts with alkenes efficiently and with high stereospecificity.

Diastereoselectivity in the intramolecular cycloaddition reactions of nitrones derived from 5-alkenals and chiral hydroxylamines

Abstract Intramolecular cycloaddition of the nitrones derived from a series of 5-alkenals and α-methylbenzyl hydroxylamine leads to mixtures of diastereomeric products in the range of 1.7/1 to 16/1. Cyclization of a series of fifteen 5-alkenyl nitrones with a chiral group on nitrogen afforded diastereomeric isoxazolidines in ratios ranging from 1.7/1 to 16/1. When R* = (S)-α-methylbenzyl, C6a of the major product was also S in those cases known.

Synthesis of the 2-aza-7-oxatricyclo[4.3.2.04,8]undecane nucleus of some gelsemium alkaloids

Abstract The preparation of a key tricyclic intermediate for the eventual total synthesis of the alkaloids gelsemicine and gelsedine is described.

Face selectivity in the [2+2] photoannelation of chiral 3(2h)-furanones with alkenes

Abstract The photocycloadditions of a series of chiral 3(2H)-furanones with alkenes show facial selectivities which parallel the steric bulk of the furanone substituents. Selectivities approaching 50:1 are observed in some instances.

Spiro[4.5]decanes by photoannelation. Total synthesis of (−)-acorenone

Abstract An efficient synthesis of the optically active spiro[4.5]decane sesquiterpene acorenone is described. The key carbon-carbon bonds are formed by a (2+2) photochemical cycloaddition between 2,2-dimethyl-3(2H)-furanone and an alkene derived from limonene.