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The crystallization-induced diastereomer transformation of a precursor to navoximod was investigated using online HPLC and optimized with inline racemization.

A practical convergent synthesis of PI3K inhibitor GDC-0908 (1) is described. The process features a dihydrobenzothienooxepine formation via palladium-catalyzed intramolecular direct C-H arylation and a Negishi coupling to construct the key C-C bonds. We further developed a general synthesis of dihydrobenzothienooxepines in good to excellent yields via palladium-catalyzed intramolecular direct C-H arylation, which tolerates both electronically and sterically diverse substituents on the phenyl ring.

SummaryBackgroundIn the era of improving overall survival rates of malignant diseases, the impact of a previous malignancy (PM) on treatment and outcome of lung cancer (LC) remains unclear.MethodsWe reviewed all LC patients from our institution that were treated from 2004 to 2006 for the occurrence of LC with PM excluding patients with multiple primary LC.ResultsA total of 444 and 2698 LC patients with and without a history of a PM were identified (prevalence of 14.1%). PM were most often located in breast (15.5%), prostate (14.9%), bladder (9.0%) and kidney (8.8%). Compared to never smokers, patients with nicotine consumption had more often a cancer history of prostate, gastrointestinal, and the head-neck region. The median interval until diagnosis of LC was 72.2 months (range 0–537 months) with most LC diagnosed 5 years after PM diagnosis. With a similar distribution of histology, stage and localization compared to controls, NSCLC patients with PM and stage IV disease showed a favorable overall survival (p

Patients with lung cancer are at risk of developing a second primary lung cancer (SPLC). However, the characteristics of patients at risk remain largely speculative. We reviewed 2816 lung cancer patients from our institution for the occurrence of SPLC. Any SPLC was categorised as synchronous when diagnosed within 2 years of the first primary lung cancer (FPLC) and after direct histological comparison of both tumours. All other SPLCs were considered as metachronous. 139 patients developed a second malignancy including 69 nonsmall cell lung cancer (NSCLC) and 9 small cell lung cancer. The median interval for diagnosis of metachronous SPLC (n=59) after FPLC occurrence was 72 months. SPLC detected within 5 years of FPLC diagnosis had a more favourable stage distribution (p=0.02). After diagnosis of SPLC, patients had a superior median overall survival compared to controls (57.7 versus 18.1 months; p

The optically active, facial complex Cr(CO)3(PP′P″) (1) with the tridentade ligand PP′P″ = (R)-(+)-1,2,4-tris (diphenylphosphino)butane has been synthesized and characterized. The complex Cr(CO)3(PP′)P″ (PP′ = (R)-(+)-prophos, P″ = PMe2Ph) forms two pairs of diastereomers, facial (3, 4) and meridional (5, 6), respectively, that can be separated by preparative column chromatography. Surprisingly, the CD spectra of Cr(CO)3(PP′P″) (1) and the facial diastereomer of Cr(CO)3(PP′P″ (3), which have the same configuration at the Cr atom, are dissimilar. The meridional configuration of the two isomers 5 and 6 of Cr(CO)3 (PP′)PMe2Ph is supported by the 31P and 1H NMR spectra of the optically inactive complex Cr(CO)3(PP′)P″ (PP′ = 1-[di (4-methoxyphenyl)phosphinol-2-(diphenylphosphino)ethane P″ = PMePh2) which forms the meridional isomers 9 and 10.

We present the clinical and laboratory features of a boy with a new syndrome of mitochondrial depletion syndrome and T cell immunodeficiency. The child suffered from severe recurrent infectious diseases, anemia, and thrombocytopenia. Clinically, he presented with severe psychomotor retardation, axial hypotonia, and a disturbed pain perception leading to debilitating biting of the thumb, lower lip, and tongue. Brain imaging showed hypoplasia of corpus callosum and an impaired myelinization of the temporo-occipital region with consecutive supratentorial hydrocephalus. Histologic examination of a skeletal muscle biopsy was normal. Biochemical investigation showed combined deficiency of respiratory chain complexes II+III and IV. MtDNA depletion was found by real-time PCR. No pathogenic mutations were identified in the TK2, SUCLA2, DGUOK, and ECGF1 genes. A heterozygous missense mutation was found in POLG1. The pathogenic relevance of this mutation is unclear. Interestingly, a lack of CD8(+) T lymphocytes as well as NK cells was also observed. The percentage of CD45RO-expressing cells was decreased in activated CD8(+) T lymphocytes. Activation of T lymphocytes via IL-2 was diminished. The occurrence of the immunologic deficiency in our patient with mtDNA depletion is a rare finding, implying that cells of the immune system might also be affected by mitochondrial disease.

Department of Chemistry and Division of Molecular Engineering and Chemistry, Korea University, Seoul 136-701, KoreaReceived September 16, 2004Key Words : Pauson-Khand reaction, Propargyl aldehyde dicobalt hexacarbonyl, Asymmetric addition,Bis(homoallyl)zincThe preparation of the optically active secondary prop-argyl alcohols has been a subject of intensive researches.