Polyprenylated polycyclic acylphloroglucines (PPAPs) are a family of natural products that possess a wide range of different important biological activities because of the relative position and configuration of four substituents that decorate one common central bicyclo[3.3.1]nonane-2,4,9-trione core. The rigid bicyclic framework with its lipophilic side chains and its hydrophilic trione moiety represents a nature-derived lead structure that arranges the substituents (R(1) to R(4)) into a defined topographical orientation. As the substituents are responsible for the biological activities, the seven-step synthetic approach presented here sets the stage for an iterative introduction of R(1) to R(4) and thus generates structurally diverse trans-type B PPAPs. Four natural and one non-natural trans-type B PPAPs were prepared starting from acetylacetone with overall yields that ranged from 6 to 22%. The concept of separating framework construction from decorating transformations plus the minimization of protecting-group operations are the key issues for the realization of our synthetic approach.

Polyprenylated polycyclic acylphloroglucinols (PPAP) are a constantly growing class of natural products that exhibit a common bicyclo[3.3.1]nonatrione core and consist of currently more than 200 members. A subclassification among the various natural products of this class includes the position of the exocyclic acyl group, the prenylation grade of the core, and the relative configuration at C-7 within the core. About 10% of the reported structures, however, possess an additional chiral center at C-6. Herein we describe a straightforward access to guttiferone A and epi-guttiferone A, in which full control of stereoselectivity is achieved via conformational control, and a strict separation of framework decorating from framework constructing operations sets the stage for a short 13-step synthesis.

In the past 20 years, peptide-based antibiotics, such as vancomycin, teicoplanin, and daptomycin, have often been considered as second-line antibiotics. However, in recent years, an increasing number of reports on vancomycin resistance in pathogens appeared, which forces researchers to find novel lead structures for potent new antibiotics. Herein, we report the total synthesis of a defined endo-type B PPAP library and their antibiotic activity against multiresistant S. aureus and various vancomycin-resistant Enterococci. Four new compounds that combine high activities and low cytotoxicity were identified, indicating that the PPAP core might become a new non-peptide-based lead structure in antibiotic research.

Carbohydrates are an omnipresent class of highly oxygenated natural products. Due to their wide spectra of biological activities, they have been in the center of synthetic organic chemistry for more than 130 years. During the past 50 years non-natural carbohydrates attracted the interest of various chemists in the fields of organic, biological, and medical chemistry. Especially desoxygenated sugars proved to be an important class of compounds. Up to date, most non-natural analogues are synthesized starting from natural, enantiomerically pure carbohydrates in multistep synthesis. In this report, we present a synthetic strategy that allows the selective modular synthesis of natural and non-natural carbohydrates within five synthetic steps starting from readily available starting materials. Due to a sequential introduction of O- or N-functionalities, a regioselective protection of each new functional group is possible. The key step in the carbohydrate synthesis is a RuO4-catalyzed oxidative cyclization via a pH-dependent dehydrogenation-dihydroxylation-cyclization or an oxidative fragmentation-cyclization, leading to highly substituted new carbohydrates, in which each functional group is orthogonally protected and accessible for further synthetic operations.

Carbohydrates U 0500 A General, Iterative, and Modular Approach Toward Carbohydrate Libraries Based on Ruthenium-Catalyzed Oxidative Cyclizations. -(NIGGEMANN, M.; JELONEK, A.; BIBER, N.; WUCHRER, M.; PLIETKER*, B.; J. Org. Chem. 73 (2008) 18, 7028-7036; Inst. Org. Chem., Univ. Stuttgart, D-70569 Stuttgart, Germany; Eng.) -Lindner 51-192