Chemical Synthesis

We wish to report here our initial efforts toward the total synthesis of the potent antitumor agent dictyostatin, describing a short and efficient synthesis of the C11–C23 fragment. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

The stereocontrolled synthesis of β-galactosyl-5-aza-sphinganines was accomplished with high efficiency by a novel and convergent strategy. The truncated β-galactosphinganine 5 was easily acylated with different long chains. Moreover, the simple conversion of thiazole to formyl enabled 5-aza-alkylchains to be introduced via an amino-reduction reaction. The overall yield for the synthesis of β-galacto-5-aza-sphinganines 9 and 13 was about 30–35% starting from

Ion exchange reactions between the Dion-Jacobson-type, triple-layered perovskite RbCa2Nb3O10 and calcium, strontium, and barium cations were investigated. Exchange occurs in all systems, but only the strontium and barium systems form stable compounds. The final products, Rb1−xSrx/2Ca2Nb3O10 (x = 0.45) and Rb1−xBax/2Ca2Nb3O10 (x = 0.55), are isostructural with the parent. Unit cells contract upon replacement of rubidium with the smaller, more highly charged cation. The effect of layer contraction in directing the extent of exchange is discussed.

A complete set of platinum(II) solketal substituted phthalocyanines has been synthesized and characterized. To evaluate their potential as Type II photosensitizers for photodynamic therapy, comparative studies of their photophysical and photochemical properties with analogous zinc(II) series have been achieved: electronic absorption, fluorescence quantum yields, lifetimes, and fluorescence quenching by benzoquinone, as well as singlet oxygen generation and photodegradation. It appears that platinum(II) phthalocyanines are worth being used as Type II photosensitizers, as they exhibit good singlet oxygen generation and appropriate photodegradation.

The preparation of 2-triazolyl- and 2-triazolylmethylpyrrolidines from L-proline and L-trans-4-hydroxyproline is described, along with their evaluation as chiral ligands in ruthenium-catalyzed asymmetric transfer hydrogenation. Modular evolution of the ligands by introduction of remote substituents is also presented, showing a surprisingly important effect on the performance of the ligands.

Some 35 years ago, I had the good fortune to be accepted into Ray Wu’s lab as a graduate student. Ray was already well known for his pioneering studies in DNA sequencing, and his lab was quietly humming with the excitement of the new approaches being developed for DNA labeling, sequencing and synthesis. Looking back, I am somewhat surprised that Ray accepted me into his lab-I was not a chemistry or biochemistry student, and I was transferring from another Department where I had become disillusioned with the prospects for completing a thesis project (of my own naïve design). I’d like to briefly recount the story of how I came to work for Ray, as I think it sheds some light on his personality, in particular the importance that he placed on the support and teaching of young, inexperienced students. If he saw potential in someone, he would do whatever it took to provide the opportunities and resources for that person to develop as a scientist. John Stiles, a fellow graduate student, and I had come up with what was, in 1973, a technically challenging but novel approach to the detection of a specific mRNA. The idea was based on the recent completion of a short stretch of the DNA sequence of the yeast iso-cytochrome c gene, which had been determined by the remarkable strategy of sequencing the protein products of a series of frameshift mutants (in Fred Sherman’s lab, in nearby Rochester, N.Y.). We felt that it should be possible to chemically synthesize a DNA probe that would allow us to detect the gene and its mRNA by hybridization. But how could we actually do this? The genetic tools for the project were available in Fred Sherman’s lab, but the chemical synthesis of DNA oligonucleotides was still a significant undertaking back then. Looking around at the Cornell faculty of the time, it seemed to us that Prof. Wu’s laboratory was the best and probably the only place that this project could be carried out. But would the famous Prof. Wu listen to a couple of unknown graduate students pushing a wild plan? It was with some trepidation that John and I went to see Prof. Wu, and nervously tried to explain the idea we had come up with. Fortunately, Ray was indeed intrigued by the idea. Although our proposal must have seemed somewhat obvious to him, Ray smiled and nodded and said that it sounded “very interesting” (only later would I learn what high praise this was coming from Ray Wu!). Eventually, Ray agreed to help us carry out our plan, and to arrange the necessary collabora

Tripodal peptide analogues were designed on the basis of the phosphotyrosine binding pocket of the Src SH2 domain and assayed for their ability to bind to fluorescein-labeled phosphopeptides. Fluorescence polarization assays showed that a number of amphipathic linear peptide analogues (LPAs), such as LPA4, bind to fluorescein-labeled GpYEEI (F-GpYEEI). LPA4 was evaluated for potential application in cellular delivery of phosphopeptides. Fluorescence microimaging cellular uptake studies with fluorescein-attached LPA4 (F-LPA4) alone or with the mixture of LPA4 and F-GpYEEI in BT-20 cells showed dramatic increase of the fluorescence intensity in cytosol of cells, indicating that LPA4 can function as a delivery tool of F-GpYEEI across the cell membrane. Fluorescent flow cytometry studies showed the cellular uptake of F-LPA4 in an energy-independent pathway and confirmed the cellular uptake of F-GpYEEI in the presence of LPA4. These studies suggest that amphipathic tripodal peptide analo...

Xanthophylls are oxygenated carotenoids abun-dant in the human food supply. Lutein, zeaxanthin, and cryptoxanthin are major xanthophyll carotenoids in human plasma. The consumption of these xanthophylls is directly associated with reduction in the risk of ...