[reaction: see text] Enantioselective catalysis of Diels-Alder reactions is mostly achieved by coordinating the dienophile to relatively strong chiral Lewis acids. Here we report on a novel approach employing the hydrogen-bond-mediated association of dienophiles to chiral host molecules. In a reaction forming the steroid skeleton of norgestrel, chiral amidinium ions induce 5:ent-5 ratios of up to 2.5:1. Improved and simplified amidinium catalysts may become interesting candidates to perform stereoselective transformations.

Amidines and guanidines are important functional groups in molecular recognition and host-guest chemistry. Here it is shown that lipophilic amidinium ions catalyze a cycloaddition reaction representing the key step of the Quinkert-Dane estrone synthesis. Hydrogen-bond-mediated association with the organic cation leads to an electrophilic activation of the dienophile and to enhanced rates of the Diels-Alder reaction. The observed effects are similar to those expected from mild Lewis acids. In competition experiments, amidinium catalysis favors the reaction of the less electron deficient dienophile.

Background Damage control is essential in first aid of burn lesions. The aim of the present study was to investigate whether systemic erythropoietin (EPO) administration could prevent secondary burn progression in an experimental model. Methods The burn comb model creates four rectangular burn surfaces intercalated by three unburned zones prone to progression. Twenty-one Wistar rats were randomized to a control group or to receive intraperitoneal EPO (500 units per kg) once a day for 5 days starting 45 min (EPO45min) or 6 h (EPO6h) after burn injury. Histological analyses assessing burn depth, inflammation and neoangiogenesis, planimetric evaluation of burn progression, and laser Doppler flowmetry to assess perfusion were performed after 1, 4 and 7 days. Final scarring time and contracture rate were assessed once a week. Results Burn progression was decreased significantly with EPO45min but not EPO6h; progression of burn depth stopped in the intermediate dermis (mean(s.e.m.) burn depth score 3·3(0·6) for EPO45min versus 4·7(0·3) and 5·0(0·0) for EPO6h and control respectively on day 7; P = 0·026) and the surface extension was significantly reduced (45(8), 65(4) and 78(4) respectively on day 7; P = 0·017). This was paralleled by faster re-establishment of perfusion with EPO45min (114(5) per cent on day 4 versus 85(6) and 91(3) per cent for EPO6h and control respectively; P = 0·096). The reduction in progression resulted in a decreased healing time (7·3(0·7) weeks for EPO45min versus 11·5(1·0) and 10·8(0·5) weeks for EPO6h and control; P = 0·020) and contracture rate (P = 0·024). Conclusion Early EPO prevented burn progression, mainly by improved vascular perfusion.

The axially chiral amidinium ion 1 was synthesized by Suzuki cross coupling and by base induced cyclization of an amino nitrile intermediate. Receptor 1 may interact with guest molecules by three converging H-bond donors.Amidinium and guanidinium ions have been successfully applied to the construction of anion receptors 1 which cleave RNA 2 and undergo rapid transphosphorylation chemistry. 3 Chiral anion receptors are used for enantioselective complexation of guest molecules. In addition, since they can stabilize anionic transition states, the catalysis of many useful reactions by such receptors may be envisioned. In consequence, several syntheses of chiral guanidines appeared in the literature. 4 We have developed a general method for the preparation of chiral amidines (e.g. 2) based on a diastereoselective cyclization of amino nitriles. 5 We reasoned that additional hydrogen bonds between host and guest should further improve complex stability and stereoselectivity of guest recognition (Figure 2).Inspection of molecular models finally led to the target structure 1. Due to the symmetric resorcinol subunit, rotation around the biaryl axis of compound 1 cannot remove the hydroxy group from the binding site. This motion will only allow a fine tuning in host-guest structures of the receptor molecule which is completely rigid in the remaining parts.The terarylic skeleton of 1 was established by palladium catalyzed cross coupling. In the first Suzuki reaction, 6 we employed boronic acid 5 which could be prepared from MEM protected resorcinol 4 in 65 % yield (Scheme 1). Naphthalene building block 7 was accessible via perbromination of 2-hydroxynaphthalene and reduction (6), 7 followed by silylation of the hydroxyl group (90 %, Scheme 2). The sterically demanding TBDPS group proved to be essential for the selectivity of the Suzuki coupling. Using standard conditions, a clean reaction was observed leading to 70 % of biaryl 8. In contrast, THP protected analogues of 7 produced mixtures in the coupling step. After conversion of 8 into the tetrahydropyranyl ether (9, 98 %), a boronic acid was prepared from the Figure 1 Molecular models of amidinium ions 1 and 2 Figure 2 Recognition of anionic and neutral guests by three converging hydrogen bond donors Downloaded by: University of Pennsylvania Libraries. Copyrighted material.