We report the results of a sensitive K-band survey of Herbig Ae/ Be disk sizes using the 85 m baseline Keck Interferometer. Targets were chosen to span the maximum range of stellar properties to probe the disk size dependence on luminosity and effective temperature. For most targets, the measured near-infrared sizes (ranging from 0.2 to 4 AU ) support a simple disk model possessing a central optically thin (dust-free) cavity, ringed by hot dust emitting at the expected sublimation temperatures (T s $ 1000-1500 K). Furthermore, we find a tight correlation of disk size with source luminosity R / L 1 = 2 for Ae and late Be systems (valid over more than two decades in luminosity), confirming earlier suggestions based on lower quality data. Interestingly, the inferred dust-free inner cavities of the highest luminosity sources (Herbig B0-B3 stars) are undersized compared to predictions of the ''optically thin cavity'' model, likely because of optically thick gas within the inner AU.

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We present the results of an all-sky survey made with the Fine Guidance Sensor on Hubble Space Telescope to search for angularly resolved binary systems among the massive stars. The sample of 224 stars is comprised mainly of Galactic

The antimitotic sponge tripeptide hemiasterlin (1) and a number of structural analogues have been synthesized and evaluated in cell-based assays for both cytotoxic and antimitotic activity in order to explore the SAR for this promising anticancer drug lead. One synthetic analogue, SPA110 (8), showed more potent in vitro cytotoxicty and antimitotic activity than the natural product hemiasterlin (1), and consequently it has been subjected to thorough preclinical evaluation and targeted for clinical evaluation. The details of the synthesis of hemiasterlin (1) and the analogues and a discussion of how their biological activities vary with their structures are presented in this paper.

In this paper, we report the development of different synthetic routes to MK-7246 (1) designed by the Process Chemistry group. The syntheses were initially designed as an enabling tool for Medicinal Chemistry colleagues in order to rapidly explore structure-activity relationships (SAR) and to procure the first milligrams of diverse target molecules for in vitro evaluation. The initial aziridine opening/cyclodehydration strategy was also directly amenable to the first GMP deliveries of MK-7246 (1), streamlining the transition from milligram to kilogram-scale production needed to support early preclinical and clinical evaluation of this compound. Subsequently a more scalable and cost-effective manufacturing route to MK-7246 (1) was engineered. Highlights of the manufacturing route include an Ir-catalyzed intramolecular N-H insertion of sulfoxonium ylide 41 and conversion of ketone 32 to amine 31 in a single step with excellent enantioselectivity through a transaminase process. Reactions such as these illustrate the enabling impact and efficiency gains that innovative developments in chemo- and biocatalysis can have on the synthesis of pharmaceutically relevant target molecules.