Dennis C. Koester

A Pd-catalyzed approach to (1-->6)-linked C-glycosides.

A flexible and robust method for the assembly of (1-->6)-linked C-glycosidic disaccharides is presented. The key reaction is a Pd-catalyzed coupling of 1-iodo- or 1-triflato-glycals with alkynyl glycosides. Reinstallation of the native hydroxyl group pattern is achieved after selective hydrogenation of the triple bond using Raney-nickel. Epoxidation with DMDO and reductive epoxide opening gives access to either the alpha- or the beta-derivative, depending on the hydride source.

Hybrids of sugars and aromatics: A Pd-catalyzed modular approach to chromans and isochromans.

Herein we describe the synthesis of highly substituted chromans and isochromans using carbohydrates as starting materials. The key step of our synthetic approach is the annelation of the benzene moiety via a highly efficient Pd-catalyzed domino reaction. This powerful approach led to a small library of highly substituted chromans and isochromans by making use of a variety of different diynes and bromoglycals. We investigated several Pd-catalysts in order to improve the yields and to enlarge the scope of the domino reaction. Furthermore, we elucidated the mechanistic picture of the reaction with isotope-labelling experiments. Most probably the reaction proceeds via an oxidative addition followed by two carbopalladation steps and a final cyclization reaction.

Sonogashira-Hagihara reactions of halogenated glycals.

Summary Herein, we report on our findings of the Sonogashira–Hagihara reaction with 1-iodinated and 2-brominated glycals using several aromatic and aliphatic alkynes. This Pd-catalyzed cross-coupling reaction presents a facile access to alkynyl C-glycosides and sets the stage for a reductive/oxidative refunctionalization of the enyne moiety to regenerate either C-glycosidic structures or pyran derivatives with a substituent in position 2.

Creating Aldols Differently: How to Build up Aldol Products with Quaternary Stereocenters Starting from Alkynes

Among the numerous challenges presented by stereoselective synthesis there is one that especially stands out, namely the selective construction of quaternary stereocenters. In this category the ultimate challenge consists of the asymmetric synthesis of all-carbon quaternary stereocenters. In recent years interesting methods which deal with chiral auxiliaries have been developed. Today various catalytic methods are available for the synthesis of all-carbon quaternary stereocenters. Among these are Diels–Alder reactions, which use chiral Lewis acids, as well as copperand zincmediated cyclopropanations. Further catalytic methods for the construction of quaternary stereocenters make use of the Michael reaction or the intramolecular Heck reaction; in this, for the most part ligands such as BINAP guarantee good to excellent enantioselectivities and allow for the application of these reactions in the construction of many natural products. It is particularly difficult to construct all-carbon quaternary stereocenters in acyclic systems, which in contrast to cyclic systems have higher degrees of freedom and are therefore harder to fix conformationally. Here, especially aldol products with quaternary steoreocenters in the a position of the carbonyl moiety have been the focus. It is practically impossible to generate this structural motif using conventional methods owing to the difficulty in selectively synthesizing the (E)or the (Z)-enolate starting from the a,a’disubstituted carbonyl compound. Marek and co-workers have recently reported the successful enantioselective construction of this structural element. The group s early work dealt with a new retrosynthetic approach to generate homoallyl alcohols and homoallyl amines by starting from alkynes. By using a sequential multicomponent reaction they succeeded in constructing a homoallyl alcohol 2 with a quaternary stereocenter adjacent to the hydroxy moiety. In this, alkynyl sulfoxide 1 served as the starting material, which was consecutively treated with an alkyl copper species, an aldehyde, diethyl zinc, and diiodomethane to yield the desired product in high diastereoselectivity (Scheme 1).

Hot on the Trail of Trehalose: A Carbohydrate-Based Method for Imaging Mycobacterium tuberculosis

The fast and selective detection of bacteria has been a major topic in microbiology for decades. Against the background of imminent danger that emanates from many bacterial strains, fast and specific methods to detect them are a dream of mankind. Common techniques relying on bacteria culturing in nutrient media are considered too slow for the identification of perilous pathogens. Again and again, bacteria causing serious diseases have come into focus. The bacterium Yersinia pestis killed millions of people during the middle ages at the time of the plague, and spores of Bacillus anthracis have attracted attention as bio-warfare agent. Commonly, even established PCR-based assays are too slow for the detection of these bacteria. Like most bacteria B. anthracis has unique oligosaccharides on the surface of its spores. These carbohydrates are able to act as sweet traitors after corresponding anti-carbohydrate antibodies have been created. It has proved to be possible to detect B. anthracis spores in a highly selective manner by an indirect immunofluorescence assay. Recent advances in nanotechnology have aimed at a faster and more sensitive detection of bacteria by NMR. In particular Mycobacterium tuberculosis or surrogates such as Bacillus Calmette-Gu rin were targeted. Most common methods for the detection of tuberculosis are insensitive and fail in clinical settings due to complex measurement set-ups. Weissleder and co-workers have addressed this problem by developing a rapid detection technology that relies on bacteria-specific magnetic nanoparticles. They proved its clinical feasibility by the detection of tuberculosis with a simple setup. His group was able to detect as few as 20 colony-forming units in a time frame of about 30 min. With about two million fatalities each year, tuberculosis remains one of the most atrocious diseases caused by bacteria in the world. About 9 000 000 people are estimated to be infected annually. The development of new diagnostic techniques, drugs and vaccines is therefore highly desirable. Much of the toxicity of M. tuberculosis is caused by the complex cell envelope, which carries unique oligosaccharides and displays an effective permeability barrier. The thickness and the resistance of the cell envelope render the bacterium stable against harsh conditions and even against antibiotic treatment. A new approach to detecting M. tuberculosis developed by Barry and Davis makes use of essential mediators of the cellenvelope function and biogenesis namely the trehalose mycolyltransesterase enzymes (antigens Ag85A, Ag85B and Ag85C). These enzymes catalyse the transesterification reaction of trehalose (1), trehalose monomycolate (TMM; 3) and trehalose dimycolate (TDM; 2 ; Scheme 1). Trehaloses, which