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is the pyramidality of the nitrogens,20 clearly disposing the methyl groups to axial and equatorial positions. We assume the nitrogens are more nearly trigonal in 2 by analogy to most phosphonamides,19 phosphoramides, and 2-oxo-l,3,2-oxazaphosphorinanes unconstrained by small rings.21 These structural insights are valuable for the understanding of bonding in these systems and for the rational design of chiral adjuvants. Further studies on the structure and reactivity of P-stabilized anions are in progress.Acknowledgment is made to the donors of the Petroleum Research Fund, administered by the American Chemical Society, for partial support of this research. S.E.D. acknowledges the A. P. Sloan foundation for a Fellowship (1985Fellowship ( -1989. We are also grateful to the National Science Foundation (Presidential Young Investigator Award, NSF CHE-8451321) for support. Dr. Scott R. Wilson and Charlotte Stern are thanked for their help with the X-ray structure analysis. Supplementary Material Available: A listing of crystal and positional parameters, bond lengths, bond angles, and torsional angles for [Li+2~2THF]2 (24 pages). Ordering information is given on any current masthead page.(20) Sum of the angles: N(l) 346.2°; N(2) 346.4°.

This special issue of ChemBioChem contains peer-reviewed contributions devoted to "Kinases in Drug Discovery". With more than 518 kinases in the human kinome [1] and the overall costs of new drug development rapidly approaching the billion dollar mark, there is a great need for focused strategies and technologies to move kinase drug discovery forward in a more rapid and efficient manner. The major goal of this special issue is to outline trends in kinase-inhibitor research organized along the drug-discovery process. Target Identification and ValidationProtein kinases play a pivotal role in the regulation of a diverse range of cellular functions. It is therefore not surprising that abnormally elevated kinase activity can lead to various pathological conditions including proliferative diseases such as cancer, fibrosis, restenosis, psoriasis, and atherosclerosis as well as diabetes, inflammation, T-cell activation, tumor angiogenesis, osteoporosis, and platelet aggregation. The discovery and development of selective protein kinase inhibitors to treat diseases caused by the disregulation of signaling pathways has become an extremely promising and widespread approach for drug discovery. 03/2005ChemBioChem is a European journal of chemical biology; it is co-owned by a group of European scientific societies and published by WILEY-VCH. Contributions in ChemBioChem cover chemical biology and biological chemistry, medicinal chemistry, bioinorganic and bioorganic chemistry, biochemistry, molecular and structural biology, that is, research of the overlapping areas between biology and chemistry.

The asymmetric syntheses of 6-deoxyerythronolide B (1) and oleandolide (2) have been achieved, each in 18 linear steps. These syntheses demonstrate the utility of chiral β-keto imide building block 3 as a versatile building block for the aldol-based assemblage of polypropionate-derived natural products.

Both the (Z)-and the (E)-y-alkoxy-substituted allylboronates 1 and 3 have been prepared. They add to aldehydes with a diastereoselectivity generally exceeding 90% to give the syn-(2) and anti-diol derivatives 4, respectively. The structure of one of these adducts has been established by conversion into exo-brevicomin (26). Stereoselektive Synthese von Alkoholen, XX I). -Diastereoselektive Addition von y-Alkoxyallylboronsaiureestern an AldehydeSowohl (Z)-als auch (E)-y-Alkoxyallylboronsaureester 1 und 3 wurden dargestellt. Sie addieren sich an Aldehyde zu den syn-(2) bzw. anti-Diol-Derivaten 4, wobei die Diastereoselektivitaten meist 90% iibersteigen. Die Struktur eines der Addukte wurde durch Umwandlung in exo-Brevicomin (26) gesichert.In the synthesis of compounds having multiple adjacent stereocenters it is desirable to attain high diastereoselectivity in the steps that create the individual stereocenters. To achieve this in molecules with acyclic skeletons new methods are currently being developed'). Among the strategies to achieve this goal it would be optimal to create these stereocenters with the proper relative configuration concomitant with the construction of the molecular skeleton. This could be realized, e. g., by stereocontrolled aldol additions 3, or aldol-analogous reactions4). In this paper we would like to focus on a stereocontrolled generation of a 1,2-diol unit by addition of y-alkoxyallylboronates 1 and 3 to aldehydes. This reaction has been studied similarly by Wuts') independent of our own investigations6). Related studies involving other y-oxygenated allylmetal compounds have been reported 79839).According to our previous experience with the diastereoselective carbon -carbon bond formation using allylboronates'oJ') we expected that the (Z)-y-alkoxyallylboronates 1 should lead to the syn-1,Zdiols 2 on addition to aldehydes, whereas the (E)-counterpart 3 should give the anti-1,2-diols 4 with very little stereocrossover.