Rhodium-catalyzed intramolecular hydroacylation of 5- and 6-alkynals: convenient synthesis of alpha-alkylidenecycloalkanones and cycloalkenones

A novel intramolecular hydroacylation of 5- and 6-alkynals leading to alpha-alkylidenecycloalkanones was accomplished by using cationic a rhodium(I)/BINAP complex. For all cyclizations described, a single (E)-olefin isomer was obtained. At elevated temperature, hydroacylation and double bond migration of 5- and 6-alkynals proceeded in a one-pot reaction to give cycloalkenones. An intramolecular hydroacylation of a 7-alkynal was unsuccessful. This method represents an attractive new route to highly functionalized alpha-alkylidenecycloalkanones and cycloalkenones.     

Multivalent Ligands for Inducing Receptor-Receptor Interactions

To obtain enchanced and/or unique cellular responses to peptide hormones by simultaneous activation of two different receptor systems, chimera peptide hormones in which enkephalin (EK) is connected through sarcosine oligomer (n) to the message segment of neurotensin [NT(8–13)] were synthesized. Interaction of these two receptor systems was studied by receptor-binding assay and determination of cAMP and cGMP level in cytosol of NG108-15 cells. It was found that EK-12-NT(8- 13) induced specific cell response in terms of the second messenger level. The specific cell response was explained in terms of the enhancement of receptor-receptor interaction in cytosol due to activation of nearby occurring receptors of different kinds. It was also found that EK-12- NT(8-13) has a high affinity toward neurotensin receptor but a low affinity toward enkephalin receptor. To strengthen and prolong the activity of peptide hormones by simultaneous binding with two or more receptors in the target cell, enkephalin/lipid conjugates were immobilized on the surface of polymerized liposomes. It was found that multivalent ligands with a high receptor affinity were synthesized, which was sensibly influenced by the presence of a spacer chain connecting the enkephalin unit to the lipid part. It was found that the introduction of anionic charges to the polymerized liposomes strongly affected the receptor affinity of immobilized ligands.     

Kinetic studies of rigid copolymers containing 3,3′-substituted biphenyls and vinylimidazole

Kinetic studies were investigated with rigid copolymers composed of vinylimidazole (VIm) and 3,3′-substituted biphenyls. For neutral substrates, two different kinetic figures were observed by the influence of 3,3′-substituents. The second-order rate constants kinetically determined were largely enhanced by the reduction of ethanol content less than 30 vol % in contrast to the rapid decrease in viscosities of catalyst solutions. A parameter concerning the polymer conformation and the effect of hydrophobic interaction was obtained using a relationship between the kinetic constants with ethanol content. Maximum kinetic effect of electrostatic interaction appeared at about 50 mole % VIm content by attracting cationic substrates towards the COO^? group of the polymer catalyst. This maximum rate profile was nearly coincident with a curve derived by calculating the sequence distribution of the (VIm? COOH) linkage unit.     

Enantioselective synthesis of axially chiral anilides through rhodium-catalyzed [2+2+2] cycloaddition of 1,6-diynes with trimethylsilylynamides

We have developed a rhodium-catalyzed enantioselective intermolecular [2+2+2] cycloaddition of 1,6-diynes with trimethylsilylynamides for the synthesis of axially chiral anilides. The axial chirality is constructed at the formation of benzene rings with high enantioselectivity (up to 98% ee). It should be noted that the present reaction employs the readily prepared trimethylsilylynamides starting from commercially available bis(trimethysilyl)acetylene and the trimethylsilyl group of the product anilides is expected to be utilized for further functionalization.     

Parallel assembly of dipolar columns composed of a stacked cyclic tri-beta-peptide

A novel cyclic trimer of a beta-amino acid, trans-2-aminocyclohexylcarboxylic acid, was synthesized and its conformation and ability to form assemblies investigated. FT-IR and NMR measurements and computational calculations showed that this cyclic tri-beta-peptide has a C3-symmetric conformation with trans amide groups. A notable feature of the conformation is a vertical and parallel orientation of the three amide groups to the cyclic skeleton. The cyclic tri-beta-peptide was crystallized from a solution in trifluoroacetic acid-methanol (or trifluoroacetic acid-water) to yield a rod-shaped molecular assembly, as observed by TEM. The electron crystallography of the rod-shaped assembly both in suspension and in ultrathin cross-section revealed that the cyclic tri-beta-peptides were stacked up to form molecular columns, and that a two-fold screw symmetry operation along the column direction was present in the unit cell, which contained two cyclic tri-beta-peptides. This indicates that all the amide groups are oriented in the same direction. Since any two molecular columns are staggered by a quarter of a c-axis length and aligned parallel to each other, the dipole moments of the columns are aligned to enhance the strength additively in the whole assembly.     

Columnar assembly formation and metal binding of cyclic tri-beta-peptides having terpyridine ligands

[reaction: see text] A novel cyclic tri-beta-peptide having terpyridine (tpy) metal ligands was synthesized to investigate its assembly formation and metal complexation. Microscopic observation revealed that this cyclic peptide formed a rod-shaped molecular assembly. The assembly was able to bind Cu(II) because the tpy ligands covered the surface of the crystal, keeping the tpy plane parallel to the ring plane of the cyclic tri-beta-peptide.     

Furopyridines. VIII. Molecular structure and two-dimensional NMR spectral assignment of 2,14-dimethyl-8aβ-hydroxy-7,10-dioxo-5β,6β-(propano)-6α,8α-(ethanoimino)-trans-perhydroisoquinoline

This paper reports the two-dimensional nmr spectral assignment and the X-ray structural determination of 2,14-dimethyl-8β-hydroxy-7,10-dioxo-5β,6β-(propano)-6α,8α-(ethanoimino)-trans-perhydroisoquinoline V which was obtained from 7,10-dimethyl-2β-hydroxy-14-oxo-2,3-(methanoiminoethano)-3β,4β-(propano)-3,4,5,6,7,8-hexahydro-2H-pyrano[2,3-c]pyridine IV by isomerization with hydrochloric acid. Both the compounds IV and V afforded the same dimethiodide IV -2MeI, while the configurational isomer 2,14-dimethyl-8aβ-hydroxy-7,10-dioxo-5α,6β-(propano)-6α,8α-(ethanoimino)-trans-perhydroisoquinoline III gave monomethiodide III -Mel. The structures of these methiodides were also confirmed by X-ray analysis.     

Novel stereoconvergent transformation of 1,2a-disubstituted 1,2,2a,8b-tetrahydro-3H-benzo[b]cyclobuta[d]pyran-3-ones to 1,3-disubstituted 1,2,4a,9b-tetrahydrodibenzofuran-4-ols and its application to the second-generation synthesis of (+/-)-linderol A

1,2a-Disubstituted 1,2,2a,8b-tetrahydro-3H-benzo[b]cyclobuta[d]pyran-3-ones bearing an electron-withdrawing group at the 2a-position were treated with two equivalents of dimethylsulfoxonium methylide to give r-1,t-4a,t-9b-1,3-disubstituted 1,2,4a,9b-tetrahydrodibenzofuran-4-ols stereoconvergently regardless of the stereochemistry of the 1-position on the benzocyclobutapyran ring. This methodology was applied to the second-generation synthesis of (+/-)-linderol A, a melanin biosynthesis inhibitory natural product.     

Long-range electron transfer over 4 nm governed by an inelastic hopping mechanism in self-assembled monolayers of helical peptides

Well-ordered self-assembled monolayers (SAMs) were prepared on gold from helical peptides carrying a ferrocene (Fc) moiety at the N- or C-terminal end, and long-range electron transfer (ET) from Fc to gold was investigated. Electrochemical studies revealed that an inelastic hopping mechanism dominated over the superexchange mechanism in the ET reactions in the present SAMs and the dipole moment of the helix accelerated the ET reactions probably due to the lowering of the barrier height between the gold surface and peptide layer.     

Furopyridines. XVII . Cyanation,chlorination and nitration of furo[3,2-b]pyridine N-oxide

The N-oxide 2 of furo[3,2-b]pyridine ( 1 ) was cyanated by the Reissert-Henze reaction with potassium cyanide and benzoyl chloride to give 5-cyano derivative 3 , which was converted to the carboxamide 4 , carboxylic acid 5 , ethyl ester 6 and ethyl imidate 8 . Chlorination of 2 with phosphorus oxychloride yielded 2-9a , 3- 9b , 5- 9c and 7-chloro derivative 9d . Reaction of 9d with sodium methoxide, pyrrolidine, N,N-dimethylformamide and ethyl cyanoacetate afforded 7-methoxy- 10 , 7-(1-pyrrolidyl)- 11 and 7-dimethylaminofuro[3,2-b]pyridine ( 14 ) and 7-(1-cyano-1-ethoxy-carbonyl)methylene-4,7-dihydrofuro[3,2-b]pyridine ( 12 ). Nitration of 2 with a mixture of fuming nitric acid and sulfuric acid gave 2-nitrofuro[3,2-b]pyridine N-oxide ( 15 ).