Synthesis of acyclic nucleoside analogues based on 1,2,4-triazolo[1,5-a]pyrimidin-7-ones by one-step Vorbrüggen glycosylation

New acyclovir analogues were obtained by reaction of 1,2,4-triazolo[1,5-a]pyrimidin-7-ones 4a–i with (2-acetoxyethoxy)methyl acetate 5 in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) as catalyst (Vorbrüggen procedure). Coupling between compounds 4a–f and 5 led to a mixture of N3- and N4-isomers 6 and 7, respectively. On the contrary, the reaction of compounds 4g–i with 5 proceeded selectively with formation of N3-isomers only. It was found that the ratio of 6a–f and 7a–f depends on the presence or the absence of N,O-bis(trimethylsilyl)acetamide (BSA). Glycosylated products 6a–f and 7a–f underwent reversible isomerization under TMSOTf treatment. The ratio of glycosylated products of the coupling reaction between 4 and 5 was thermodynamically controlled. A similar reaction occurred if ZnCl₂ was chosen as a catalyst, although lower yields of the acyclic analogues of nucleosides were observed. The glycosylation of other purines (adenine and guanine) can be achieved via the non-BSA modification of the Vorbrüggen procedure.     

Manipulation of Shell Morphology of Silicate Spheres from Structural Evolution in a Purely Inorganic System

We have investigated the structural transformation of solid silica spheres into various more complex spherical structures including flower‐like, thick or thin nanosheet‐shelled and porous shelled spheres. In the absence of organic additives, sodium salts contained in this inorganic reaction system apparently direct the silica dissolution and regrowth of dissolved silicate at the nanometer‐scale, leading to the formation of a nanosheet network rather than solid aggregates. Subsequent removal of the salts by simple water washing results in voids in the siloxane network and a significant availability of surface silanol groups so that the resulting nanosheets and spheres composed of them possess large surface areas, pore volumes, and morphological flexibility, which can be varied by an applied stimulus. The results represent a rare example of the transformation of a simple silicate structure into a much more complex spherical structure involving a purely inorganic reaction system.     

Synthesis of 4-(N-azolyl)-3,5-dinitropyrazoles

NH-Azoles selectively substitute 4-positioned nitro group in 3,4,5-trinitro-1H-pyrazole in aqueous NaOH to furnish 4-(N-azolyl)-3,5-dinitropyrazoles.     

Regioselective Addition of Dithiophosphinic Acids to Vinyl Sulfides and Selenides: An Efficient Route Toward Functional Dithiophosphinates

Earlier unknown S‐[1‐(organosulfanyl)ethyl]‐ and S‐[1‐(organoselenyl)ethyl] dithiophosphinates were synthesized in 85–97% yields by regioselective addition of dithiophosphinic acids to diverse vinyl sulfides and selenides under mild conditions (ambient temperature, Et₂O, 3 h).     

Reverse Spin‐Crossover and High‐Pressure Kinetics of the Heme Iron Center Relevant for the Operation of Heme Proteins under Deep‐Sea Conditions

By design of a heme model complex with a binding pocket of appropriate size and flexibility, and by elucidating its kinetics and thermodynamics under elevated pressures, some of the pressure effects are demonstrated relevant for operation of heme‐proteins under deep‐sea conditions. Opposite from classical paradigms of the spin‐crossover and reaction kinetics, a pressure increase can cause deceleration of the small‐molecule binding to the vacant coordination site of the heme‐center in a confined space and stabilize a high‐spin state of its Fe center. This reverse high‐pressure behavior can be achieved only if the volume changes related to the conformational transformation of the cavity can offset the volume changes caused by the substrate binding. It is speculated that based on these criteria nature could make a selection of structures of heme pockets that assist in reducing metabolic activity and enzymatic side reactions under extreme pressure conditions.     

Optically Active Tetra‐tert‐butyl‐P5‐deltacyclene Epimers: Preparation,Spectroscopy, Dynamic Equilibriums,H/D Exchange,and Transition‐Metal Complex Chemistry

On the basis of isolated diastereomeric triorganylstannyl‐P₅‐deltacyclenes 7′ and 7′′ , almost pure enantiomers of their destannylation products 8′ and 8′′ are now available. These stereochemically inert cage chiral species contain a configurationally labile P1?H1 group that defines two epimers 8 a and 8 b of each of the enantiomers, which are connected by a rapid equilibrium. Mirror‐symmetric circular dichroism (CD) spectra of the enantiomeric cages are compatible with the identification of epimers. A simulation of the CD spectrum of the major epimer 8′a relates the cage chirality of the system to the observed chiroptical effects. Both cage epimers and two of the phosphorus cage atoms are active as ligands with respect to [M(CO)₅] fragments of Cr, Mo, and W. Four almost isoenergetic regio‐ and stereoisomers of the resulting mononuclear complexes are formed for these metals, but only one of the isomers per metal crystallized in the case of the racemic series of the complexes. The enantiopure versions of cages and cage complexes, however, did not crystallize at all, a well‐known phenomenon for chiral compounds. CD spectra of the optically active complex isomer mixtures are close to identical with the CD spectra of the related free cages and point again to the chiral cages as the dominant source of the CD effects of the complexes. [(Benzene)RuCl₂] complexes of the cage ligand 8 behave totally differently. Only a single species 12 =[(benzene)RuCl₂ ?8 b ] is formed in almost quantitative yield and the minor epimer 8 b plays the role of the ligand exclusively. The reaction works as well for the separated enantiomeric cage versions to yield the highly enriched enantiomers 12′ and 12′′ separately. An efficient kinetic resolution process was identified as the main reason for this finding. It is based on a high stereo‐ and regiochemical flexibility of the P?C cage ligand that is capable of adjusting to the specific requirements of a suitable transition‐metal complex fragment. Such ligand flexibility is regularly observed in metalloenzymes, but is a very rare case in classical and organometallic complex chemistry.     

Matrix-assisted laser desorption/ionization-post source decay fragmentation of cystine- containing amphibian peptides with novel cysteine tags

Long disulphide-containing peptides brevinins 1E and 2Ec from the skin secretion of the frog Rana ridibunda were reduced and alkylated with ten novel and three known derivatizing agents. Nine of novel reagents are maleimide derivatives. The peptides were also reduced with DTT directly onto the MALDI target without alkylation. Modified samples were subjected to MALDI-PSD study. Procedures, fragmentation patterns, fragment ion signal abundances and sequence coverage for two peptides modified with thirteen tags (or on-plate reduced) are described. The fast on-plate procedure for reduction/alkylation was applied to Rana ridibunda crude secretion, providing intensive signals of derivatized peptides. The corresponding ions may be used for the MS/MS sequencing procedure.     

Annelated Pyrrolo[1,2‐a][1,4]diazepines in Mannich Reaction

New Mannich bases were synthesized through an interaction of fused pyrrolo[1,2‐a][1,4]diazepines with secondary amines and formaldehyde. The reaction appears to be regioselective, yielding the monosubstituted products bearing N,N‐dialkylaminomethyl group at position 2 of the pyrrolodiazepine moiety.