Staphylococcus aureus synthesizes a large number of extracellular proteins that have been postulated to play a role in bacterial virulence. The proteomic approach was used to analyse the pattern of extracellular proteins of two different S. aureus strains, RN6390 and COL. Thirty-nine protein spots were identified by N-terminal sequencing or MALDI-TOF-MS. The differences of the extracellular protein patterns between both strains are striking. Among the 18 proteins identified in S. aureus COL there are nine proteins not yet discovered in S. aureus RN6390. These are enterotoxin B, leukotoxin D, enterotoxin, serin proteases (SplA and SplC), thermonuclease, an IgG binding protein and two so far unknown proteins in S. aureus with similarities to SceD precursor in Staphylococcus carnosus and to synergohymenotropic toxin precursor in Streptococcus intermedius. In contrast, lipase as well as staphylokinase identified in S. aureus RN6390 were not detectable in S. aureus COL under the same conditions. By using a regulatory mutant of sarA (ALC136) isogenic to strain RN6390 we identified five proteins positively regulated by SarA and 12 proteins negatively regulated by SarA. Besides V8 protease (StsP) and Hlb already described to be regulated by the sar locus new putatively sarA-dependent proteins were identified, e.g. glycerolester hydrolase and autolysin both down-regulated in the sarA mutant, and aureolysin, staphylokinase, staphopain and format tetrahydrofolate lyase up-regulated in the mutant. Moreover, the role of sigma B in expression of extracellular proteins was studied. Interestingly, we found 11 proteins at an enhanced level in a sigB mutant of S. aureus COL, among them enterotoxin B, alpha and beta hemolysin, serine proteases SplA and SplB, leukotoxin D, and staphopain homologues. The sigma B-dependent repression of gene expression occurs at the transcriptional level. Only one protein, SceD, was identified whose synthesis was down-regulated in the mutant indicating that its gene belongs to the sigma B-dependent general stress regulon.

Enantiopure diarylmethanols and diarylmethylamines are important intermediates for the synthesis of pharmaceutically relevant products with antihistaminic, antiarrhythmic, diuretic, antidepressive, laxative, local-anesthetic and anticholinergic properties. Furthermore, they have been used as precursors for 1,1-diarylalkyl moieties, which occur in other antidepressants as well as in antimuscarinics and endothelin antagonists. In this critical review catalytic strategies towards enantioenriched diarylmethanols and diarylmethylamines are discussed, including methods for asymmetric carbon-carbon bond formations by aryl transfer reactions to aldehydes and arylimines, respectively, and enantioselective reductions of diarylketones.

Chiral diaryl methanols are important intermediates for the synthesis of biologically active compounds. Here, we describe a flexible method for their catalyzed asymmetric synthesis from readily available starting materials. Noteworthy is the fact that with a single catalyst both enantiomers of the product are accessible simply by choosing the appropriate combination of aryl boronic acid or aldehyde as aryl donor and acceptor, respectively. The catalysis with a planar-chiral ferrocene is easy to perform and yields a broad range of products with excellent enantioselectivities (up to 98% ee).

In strongly basic media, the [nido-B11H14]- anion reacts with the haloforms. Dehydrogenation to [closo-B11H11]2- is the only reaction observed with iodoform. With chloroform and bromoform, the cage is expanded by dihalocarbene insertion. The dominant products are the [closo-CB11H12]- and the [2-Br-closo-CB11H12]- anion, respectively. The chief side product is the [closo-B11H11]2- anion, which results from dehydrogenation of the starting material. It was identified by 11B NMR spectroscopy and isolated after acidic aqueous workup in the form of the [nido-7-OH-B11H13]- anion. Since the starting [nido-B11H14]- anion is available from NaBH4 and BF3·Et2O in 50% yield, its conversion to [closo-CB11H12]- with chloroform and base in a 40% yield represents a useful laboratory route to the numerous known but previously very expensive derivatives of [closo-CB11H12]-, highly prized for their very low nucleophilicity.

Several sulfoximines have been arylated in good to high yield by palladium catalysis using aryl nonaflates and aryl triflates. Moreover, the successful synthesis of N-aryl sulfoximines from aryl tosylates is described using a Ni(COD) 2 /BINAP catalyst.Palladium-catalyzed processes which employ aryl or vinyl sulfonates 1 are becoming increasingly attractive, because they are easily accessible from the corresponding phenols and ketones, respectively, thus allowing an entirely different class of substrates -other than aryl or vinyl halides -to be utilized as starting materials. For example, aryl triflates have been widely used in Heck 2 and SuzukiMiyaura 3 type couplings and more recently, they have also been employed in the palladium-catalyzed synthesis of aryl amines. 4 An important improvement for the latter transformation was achieved when NaOt-Bu -which was responsible for the formation of large amounts of hydrolytic byproducts of the aryl triflate 5 -was replaced by cesium carbonate. This mild base led to both an increased functional group tolerance and a dramatically decreased rate of the hydrolysis of the triflate precursors. 6 Compared to aryl triflates, the corresponding nonaflates are even more attractive substrates because they display a higher reactivity and a more pronounced stability towards hydrolysis. 7 Despite of all of these positive characteristics of aryl sulfonates, palladium-catalyzed aminations of aryl sulfonates with sp 2 -hybridized nitrogen nucleophiles other than benzophenone imine are still rare. 8Recently, we established a novel method for the catalytic N-arylation of sulfoximines with aryl bromides and aryl iodides which has already been applied by Harmata and Parvi in the synthesis of benzothiazines. 9,10 In this protocol Pd(OAc) 2 /BINAP serves as catalyst and cesium carbonate acts as base allowing for mild reaction conditions and broad functional group tolerance (Scheme 1).Herein, we report on the extension of this sulfoximine N-arylation method first, to palladium-catalyzed reactions of sulfoximines with aryl triflates and aryl nonaflates and second, to nickel-catalyzed couplings of sulfoximines and aryl tosylates. (2) under essentially identical reaction conditions as for couplings of aryl bromides, led to the formation of the corresponding products in good to high yields (Table, Entries 1-5). Interestingly, the substrate which is most susceptible toward hydrolysis -4-nitrophenyl triflate -gave the highest yield of coupling product 7 at 86% indicating that triflate hydrolysis is no serious side reaction. Aryl nonaflates 7,11 reacted also smoothly in the presence of a catalytic amount of Pd(OAc) 2 /BINAP affording the corresponding N-aryl sulfoximines in good to high yields (Table, Entries 6-8). For example, N-(4-tert-butylphenyl) S-methyl-S-(p-tolyl) sulfoximine was obtained with a yield of 76%, which is remarkable taken into account that this compound is formed in only 67% yield from the corresponding aryl bromide. As in reactions with aryl triflates electron-deficient aryl nonaf...

Small amounts of simple methoxy poly(ethylene glycol)s (MPEGs) have a beneficial effect on catalyzed asymmetric aryl and alkyl transfer reactions onto aldehydes. The enantiomeric excesses of the products are improved, and this "MPEG effect" allows a reduction of the catalyst loading by a factor of 10.

[reaction: see text] Contrary to expectations, commercially available 2 M Me2Zn in toluene is able to promote the addition of phenylacetylene to aldehydes and ketones. This reactivity is determined by a new, unprecedented mechanism, which involves activation of the zinc reagent via coordination with carbonyl substrates that behave "ligand like". Broad scope, high tolerance to functional groups, and a simple procedure make this new method highly interesting for the synthetic chemist.

The addition of Ph(2)Zn to aldehydes has been investigated by DFT calculations. The experimentally observed increase in enantioselectivity upon addition of Et(2)Zn to the reaction mixture is rationalized from calculations of all isomeric transition states. Spectator ethyl groups in the transition state do not lower the intrinsic activation barrier, but instead increase it. In the presence of a bulky ligand, the inherently preferred all-phenyl transition state is selectively disfavored. The paths with less sterically demanding spectator ethyl groups will experience a more drastic ligand acceleration, and thus the influence of the ligand would be expected to be stronger in the presence of Et(2)Zn, in agreement with experimental observations.