Ring-closing alkyne metathesis approach toward the synthesis of alkyne mimics of thioether A-, B-, C-, and DE-ring systems of the lantibiotic nisin Z

[reaction: see text] Ring-closing alkyne metathesis toward the synthesis of the alkyne-brigded A-, B-, C-, and (D)E-ring mimics of the peptide antibiotic nisin Z is described. We have successfully synthesized alkyne-bridged cyclic peptides containing 4-7 amino acid residues in yields ranging from 18 to 82%.     

Evolutionary chemistry approach toward finding novel inhibitors of the type 2 diabetes target glucose-6-phosphate translocase

A genetic algorithm (GA), driven by experimentally determined biological activities as a feedback fitness function, was used to propose novel small molecules as inhibitors of glucose-6-phosphate translocase (G6PT) in iterative rounds of evolutionary optimization. A straightforward polymer-supported synthetic sequence was implemented to synthesize molecules proposed by the GA, and the biological activities of the compounds were determined by a microsomal assay. Additional compound design strategies were integrated, such as Tanimoto similarity-based selection of starting materials and transfer of favored structure elements into a new chemical scaffold to identify more active and selective inhibitors.     

Identification of Tmem10/Opalin as a novel marker for oligodendrocytes using gene expression profiling

Background  

During the development of the central nervous system, oligodendrocytes generate large amounts of myelin, a multilayered insulating membrane that ensheathes axons, thereby allowing the fast conduction of the action potential and maintaining axonal integrity. Differentiation of oligodendrocytes to myelin-forming cells requires the downregulation of RhoA GTPase activity.     

Mesophase behaviour and thermal stability of octa-alkoxy substituted phthalocyaninatocobalt (II) complexes

Cobalt (II) phthalocyanines substituted with eight alkoxy chains in the peripheral (2, 3, 9, 10, 16, 17, 23, 24) positions were prepared. The alkoxy chain length was varied between n-butyloxy (C₄H₉O) and n-octadecyloxy (C₁₈H₃₇O). Studies by polarizing optical microscopy and high temperature X-ray diffraction revealed that all the complexes are liquid crystalline and that they exhibit a hexagonal columnar mesophase (Col_h). Transition enthalpies were determined by differential scanning calorimetry. The clearing point could only be observed for compounds with a chain length longer than C₁₃H₂₇O. Both the melting and clearing points decrease with increasing chain length. The transition temperatures of these discotic metallomesogens are higher than those of the corresponding metal-free phthalocyanines, but are comparable with those of the corresponding copper (II) compounds. The thermal decomposition of the compounds was studied by thermogravimetry.     

Classical Klingenberg generalized quadrangles

Research supported by I.W.O.N.L. grant no. 840037.     

Reactions of n-sulfinyl-p-toluenesulfonamide with alcohols

N-Sulfinyl p-toluenesulfonamide (1) reacted with triaryl- and diarylmethanols to give predominantly N- substiuted sulfonamides and SO₂ presumably via carbonium ion intermediates. When carbonium ion forming alchols, such as t-BuOH and Ph₂C(Me)OH, were used the predominant products were alkenes and p- toluenesulfonamide. Allytic alcohols afforded N- substiuted sulfonamides along with dienes andp-toluenesulfonamide. Alcohols which could not predictably give relatively stable intermediate carbonium ions, gave either dialkyl sulfites or dialkyl eithers, along with p-toluenesulfonamide. In one case, namely with 9-phenylfluorenol the 1:1 adduct with 1 (an amidosulfite) was isolated. A mechanism for the reactions is proposed.