Synthesis of dehydroxy-trans-resorcylide by intramolecular alkylation of the protected cyanohydrin using a butadiene telomer as a building block

Dehydrroxy-trans-resorcylide ($\text{15}$) was synthesized by efficient intramolecular alkylation of the protected cyanohydrin. The butadiene telomer obtained by the palladium catalyzed reaction of butadiene with acetic acid was used as a suitable block of the carbocycle.     

Multipoint recognition of catecholamines by hydrindacene-based receptors accompanied by the complexation-induced conformational switching

The molecular recognition of catecholamines by hydrindacene-based receptors 1 and 2, as well as the durene-based receptor 3, and the guest-induced conformational changes are reported. These receptors selectively bind adrenaline and dopamine salts through the guests' ammonium group and 3-hydroxyl group on the aromatic ring. In the case of adrenaline, an additional hydrogen bond with a benzylic hydroxyl group is formed. In 2 % CD3CN/CDCl3, the association constants are of the order of 10(4) M(-1), which is much larger than with guests without the 3-hydroxyl groups (10(3) M(-1)). The two amide groups of receptor 1 can rotate freely around the C(aromatic)--C(amide) bond, whereas the tert-amide in 2 changes between two stable conformations at a slow enough rate to allow detection by (1)H NMR spectroscopy. In the absence of a guest molecule, the syn-conformer is less stable than the anti-conformer. On complex formation with adrenaline, the syn-conformer becomes dominant due to an intramolecular dipole-reversal effect in addition to multipoint hydrogen bonding.     

Determination of threo and erythro configurations of 3-fluorophenylalanine for verifying stereochemical aspects of recently reported syntheses

Determination of threo and erythro configurations of both diastereoisomers of 3-fluorophenylalanine on the basis of chemical transformation and X-ray analysis has confirmed that the aziridine ring opening reaction gives the threo isomer stereoselectively, whereas the fluorodehydroxylation reaction affords both isomers nonselectively.     

Kinetic stabilization of the [1.1]paracyclophane system: isolation and X-ray structural analysis of a [1.1]paracyclophane derivative and its interconversion with the transannular adduct

Intentionally designed kinetic stabilization of the [1.1]paracyclophane skeleton has been achieved by multiple substitution of the aromatic rings with trimethylsilylmethyl and N,N-dimethyl-carbamoyl groups, which serve to shield the proximate bridgehead carbon atoms sterically from access by other reagents. The bis(Dewar benzene) precursor (1a) has been prepared in essentially the same manner as previous derivatives--starting from the photocycloaddition of 1,4-bis(trimethylsilyl)-2-butyne to octa-hydroindacene-1,5-dione--except for a few critical modifications described in the text. Substituted [1.1]paracyclophane (2a), photochemically generated from the precursor, is indefinitely stable at 50 degrees C and suffers decomposition only by 8 % after 2 h at 100 degrees C in degassed n-decane, demonstrating its greatly improved kinetic stability compared to previous [1.1]paracyclophanes. Since 2a undergoes efficient photochemical transformation into the transannular addition product 3a, irradiation of la tends to produce a mixture of products consisting mainly of 3a. Compound 3a, however, reverts thermally to 2a in a process of half life 40 min at 55 degrees C; the activation parameters for this process are deltaH(not equal to)= 21.1 +/- 0.8 kcalmol(-1) and deltaS(not equal to) = -10.5 +/- 2.6 cal K(-1)mol(-1). Thus, on heating 3a in benzene and cooling the resultant solution, 2a is obtained as orange-red crystals. X-ray crystallographic analysis of 2a reveals benzene rings bent to the highest degree ever reported for a paracyclophane, with their face-to-face arrangement in unusually close proximity. The shortest nonbonding interatomic distance is 2.376 A; less than the sum of the van der Waals radii by more than 1.0A. The generation of related substituted [1.1]paracyclophanes and their kinetic stabilities are also reported.     

Elimination of the 4-hydroxyl group of the alkaloids related to morphine—I

Sinomenine, an alkaloid of the Japanese plant Sinomenium acutum, was converted to the 4-phenylether by the Ullmann reaction in a good yield. The Clemmensen reduction of sinomenine-phenylether and of its derivatives gave (+)-3-methoxy-4-phenoxy-N-methyl-Δ^x-morphinan.

Hydrogenation and successive sodium-liquid ammonia reduction of (+)-3-methoxy-4-phenoxy-N-methyl-Δ^x-morphinan gave (+)-3-methoxy-N-methylmorphinan.     

Organic synthesis by means of noble metal complexes—XCIV : Palladium catalyzed hydrosilylation of monoenes and conjugated dienes

Palladium compounds and metallic palladium combined with phosphine are active catalysts of selective hydrosilylation of terminal olefins. Butadiene and trichlorosilane give a 1:1 adduct and trimethylsilane affords a 1:2 adduct. Special features of the palladium catalyzed hydrosilylation reactions are presented.     

Oxidative cleavage reactions of catechol and phenol to monoester of cis,cis,-muconic acid with the oxidizing systems of O2/CuCl,KOH/CuCl2

Oxidative cleavage reactions of catechol with CuCI to give monoester of cis,cis-muconic acid in pyridine containing alcohol was investigated under various conditions. The same oxidation was carried out also with the systems of KO₂/CuCl₂ and KOH/CuCl₂ in pyridine containing alcohol in the absence of oxygen. Phenol was oxidized with the same oxidizing systems to give the same monoester of muconic acid.     

Distribution of pirarubicin in human blood.

We investigated the distribution and stability of pirarubicin in human blood obtained from 12 healthy volunteers. The distribution of pirarubicin into blood cells showed marked temperature- and concentration-dependencies and the Arrhenius plot for pirarubicin uptake in blood was biphasic. Therefore, pirarubicin appears to be taken up into blood cells by a carrier-mediated system. Pirarubicin was mainly enzymatically metabolized to pirarubicinol in blood cells, but pirarubicin was not metabolized into doxorubicin in either blood or plasma. On the other hand, in plasma, pirarubicin was degraded to unknown inactive compounds instead of pirarubicinol. It is therefore suggested that blood cells serve to protect against the degradation of pirarubicin into inactive compounds in blood. Accordingly, when the monitoring of pirarubicin and its active metabolites is carried out in patients, both blood and plasma must be frozen immediately after blood collection.     

Preparation of substituted benzoyltrimethylsilanes by the palladium-catalyzed silylation of substituted benzoyl chlorides with hexamethyldisilane

A direct preparative route to benzoyltrimethylsilane has been found by the reaction of benzoyl chloride with hexamethyldisilane in the presence of a specified palladium(II) complex as catalyst.     

Elimination of the 4-hydroxyl group of the alkaloids related to morphine—II

Dihydrothebaine-φ, dihydrothebainone-Δ⁵-enol methylether and dihydrothebainone were converted to the respective 4-phenylethers by Ullmann reaction in good yields. These phenylether derivatives were reduced to 4-desoxy compounds by sodium-liquid ammonia reduction.

Clemmensen reduction of the phenylether and the desoxy derivatives gave (-)-3-methoxy-4-phenoxy-N-methyl-morphinan and (-)-3-methoxy-N-methylmorphinan respectively.