The novel decalin-type N,O,P-heterocycles, P(3)-axially and P(3)-equatorially substituted cis- and trans-configurated 3-fluoro-2,4-dioxa-7-aza-, 2,4-dioxa-8-aza-, and 2,4-dioxa-9-aza-3-phosphabicyclo[4.4.0]decane 3-oxides, are configuratively fixed and conformationally constrained phosphorus analogues of acetylcholine. The compounds are suitable probes for the investigation of molecular interactions with acetylcholinesterase.

Phosphorylation of suitable piperidine precursors yielded a series of novel decalin-type O,N,P-heterocycles. The title compounds, P(3)-axially and P(3)-equatorially X-substituted, cis- and trans-configurated 2,4-dioxa-7-aza-, 2,4-dioxa-8-aza-, and 2,4-dioxa-9-aza-3-phosphabicyclo[4.4.0]decane 3-oxides (X = Cl, F, 4-nitrophenoxy, and 2,4-dinitrophenoxy), are configuratively fixed and conformationally constrained P-analogues of acetylcholine and as such represent acetylcholine (7-aza and 9-aza isomers) or gamma-homo-acetylcholine mimetics (8-aza isomers). Being irreversible inhibitors of acetylcholinesterase (AChE), the compounds are considered to be suitable probes for the investigation of the stereochemical course of the inhibition reaction by P-31-NMR spectroscopy. Moreover, the design of these mimetics will enable studies of molecular interactions with AChE, in particular, the recognition conformation of acetylcholine.

Each year corrosion induced damages amount to billions of Dollars. Not only does the weather and other environmental determinants favor the corrosion of metal surfaces but microorganisms accelerate and often even induce this costly abrasion through their metabolic activity. Nonetheless, the microbial communities that live on metals were scarcely investigated, so far, and there is still a lack of foolproof and quick methods for examining them. Our course project deals with the molecular analysis of corrosion inducing bacterial biofilms growing on metal surfaces. It is part of an ongoing research project on Corrosive Biofilm formation, see: http://www.microeco.unizh.ch/projects/indexpro.htm

Continuing our investigations (poster1, 2) concerning the irreversible inhibition of serine-hydrolases (acetylcholinesterase, chymotrypsin) by organophosphates [1][2] we have prepared the racemic 3-fluoro-2,4-dioxa-3l5-phosphabicyclo[4.4.0]decan-3-ones (±)-7-(±)-12. Being conformationally restricted, these cis- and trans-decalinetype congeners with the F-substituent in the axial and equatorial position fit differently into the active site of acetylcholinesterase (AChE) as represented by their kass-values.

The compound (E,E)-1,3-bis(3'-hydroxyprop-1'-enyl)benzene, obtained by reduction of (E,E)-1,3-bis[2'-(methoxycarbonyl)ethenyl]benzene with diisobutylaluminum hydride, was selectively transformed into 1,3-bis[(1'S,2'S)-1',2'-epoxy-3'-hydroxypropyl]benzene by a Sharpless oxidation. After protection of the hydroxyl groups as their TBDMS ethers, the epoxide rings were selectively opened by reacting them with LiPPh2 and the resulting diphosphine, after reaction with elemental sulfur,gavel,3-bis[(1'S,2'S)-1'-(diphenylthiophosphinyl)-2',3'-dihydroxypropyl]benzene. After conversion to the corresponding bis(dioxolane), the latter compound was desulfurized using P(n-BU)3. The overall yield of the ligand precursor, 1,3-bis[(1'S,2'S)-1'-(diphenylphosphino)-2',3'-O-isopropylidene-2',3'-dihydroxypropyl]benzene, based on the commercial isophthalaldehyde starting material used, was ca. 30%. The complex [2,6-bis[(1'S,2'S)-1'-(diphenylphos-phino)-2',3'-O-isopropylidene-2',3'-dihydroxypropyl]phenyl]chloroplatinum(II) (18) was obtained by reacting the above ligand precursor with [Pt2(mu-Cl)2(eta3-CH2C(CH3)CH2)2]. The X-ray crystal structure of [2,6-bis[(1'S,2'S)-1'-(diphenylphosphino)-2',3'-O-isopropylidene-2',3'-dihydroxy-propyl]phenyl[(eta1-nitrato)platinum(II) (19) obtained from 18, by reacting it with AgNO3, was determined. Its structural features are closely related to those of the corresponding compound in which the dioxolane unit has been replaced by a methyl group. Crystals of 19.toluene are orthorhombic, space group P2(1)2(1)2(1), Z = 4, a = 10.160(1) angstrom, b = 15.721(2) angstrom, and c = 28.799(2) angstrom. The corresponding triflato complex, obtained by reacting the chloro compound 18 with silver triflate, was used as catalyst precursor (1-2 mol %) in the aldol reaction of aldehydes with methyl isocyanoacetate in the presence of a cocatalytic amount of NEti-Pr2. Enantioselectivities up to 65 % were obtained for the major diastereoisomeric trans-oxazoline product, whereas the overall catalytic activity was comparable to that of known systems.

Equimolecular amounts of the ligands (1S,1'S),(1R,1'R)-1,3-bis[l-(diphenylphosphino)ethyl]benzene, rac-form, and of the corresponding meso-form, were obtained by two methods. The first involved the reaction of 1,3-bis[(diphenylthiophosphino)methyl]benzene (1) with n-butyllithium followed then with methyl iodide, (2) separation of the rac- and meso-forms of the products by fractional crystallization, and (3) their desulfurization with tri-n-butylphosphine. In the second method the methylation reaction was carried out on 1,3-bis[(diphenylphosphino)methyl]benzene-bisborane and the borane removed from the products by reaction with diethylamine. The complexes rac-[(1S,1'S),(1R,1'R)-1,3-bis[1-(diphenylphosphino)ethyl]phenyl]chloroplatinum(II), 9a,b, and the corresponding meso-form, 9c, were obtained by reacting the respective phosphines either with cis-[PtCl2(Pph3)2], followed by elemental sulfur, or with [Pt2(mu-Cl)2(eta3-2-MeC3H4)2]. Reaction of the above complexes with AgCF3SO3 gave the corresponding trifluoromethanesulfonates while the action of AgPF6 and (R)-methyl-4-tolyl sulfoxide gave the corresponding sulfoxide complexes as their PF6 Salts, 24a,b and 24c, respectively. The pure isomeric forms 24a and 24b could not be obtained by fractional crystallization. The complex [2,6-bis[(diphenylphosphino)methyl]phenyl]methylplatinum, when reacted with methyllithium, followed by methyl iodide, gave a mixture of rac-[(1S,1'S),(1R,1'R)-2,6-bis[l-(diphenylphosphino)ethyl]phenyl]methylplatinum 21a,b, and the corresponding meso-form, 21c, in ratios varying between 14 and 37 % of the former and the remainder of the latter, depending on the reaction temperature. Similar results were obtained when LDA was used as a base. Deprotonation of either pure 21a,b and 21c with methyllithium, followed by hydrolysis, gave isomeric mixtures with ratios corresponding to those quoted above. However, when LDA was used for this reaction, 21a,b was obtained in 45% yield. The X ray crystal structures of [2,6-bis[(diphenylphosphino)methyl]phenyl]chloropalladium, 7a, and. of 9a,band 9c are reported. Their structural features are very similar to those of several related compounds, the only significant difference between 9a,b and 9c being the steric repulsion between a terminal phenyl group and the equatorial methyl substituent in the latter compound.

AbstractThe use of [Pd(H2O)2(Ph2PCH2CH2PPh2)] (CF3SO3)2 as a catalyst for the acetalisation of a variety of aldehydes and ketones and for trans‐acetalisation is described. It is also shown that Pt(H2O)2(PH2PCH2CH2PPh2) (CF3SO3)2 is at least as effective as the corresponding Pd compound, while much lower reaction rates are observed with [Rh(MeOH)2(Ph2PCH2CH2PPh2)] [BF4].

AbstractAs demonstrated for (I) with methanol, the use of the Pd complex as a catalyst for the acetalization of a variety of aldehydes and ketones and for trans‐acetalization is described (table, 20 examples).