Mechanistic studies in the reaction of 4-phenyl-1,2,4-triazoline-3,5-dione with 2,5-dimethyl-2,4-hexadiene

Secondary isotope effect measurements of methanol adducts from the reaction of 4-phenyl-1,2,4-triazoline-3,5-dione with 2,5-dimethyl-2,4-hexadiene, support the formation of an aziridinium imide intermediate rather than an open dipolar intermediate in the rate determining step.     

n-median semilattices

An n-median semilattice (n3) is a meet-semilattice such that (i) every principal ideal is a distributive lattice and (ii) any n-element set of elements is bounded above whenever each of its (n-1)-element subsets has an upper bound. A 3-median semilattice is thus a median semilattice in the classical sense. In this note we demonstrate how the characteristic features of median semilattices carry over to the more general case of n-median semilattices.Research supported in part by ONR Grant N00014-90-1008.     

An algebraic setting for near-unanimity consensus

Some sets of taxonomic models can be structured as meet-semilattices having the properties that (i) every principal ideal is a distributive lattice and (ii) each finite subset has an upper bound whenever each of its (n–1)-subsets is bounded above, where n3 is a fixed number. Every such semilattice is endowed with an n-ary near-unanimity operation. We show that for n4 one can define these semilattices solely in terms of this n-ary operation. The resulting algebras are subdirect powers of two-element algebras, and of course, generalize median algebras.     

Short and versatile route to a key intermediate for lactacystin synthesis

[reaction: see text] A key intermediate 14 for the synthesis of lactacystin 1 has been constructed in four steps and 33% overall yield. The key steps involve cyclization of a suitably functionalized glutamic acid derivative and concomitant alkylation of the resulting beta,beta-diketoester system, C-acylation of the cyclic alpha-amidoketone 9, and decarboxylbenzylation of 12. Alkylation of a related beta,beta-diketoester 5 was additionally achieved with several electrophiles.     

Coordination properties of Cu(II) and Ni(II) ions towards the C-terminal peptide fragment -TYTEHA- of histone H4

In order to reveal more information about the toxicity caused by metals and furthermore their influence to the physiological metabolism of the cell, the hexapeptide model Ac-ThrTyrThrGluHisAla-am representing the C-terminal 71-76 fragment of histone H4 which lies into the nucleosome core, was synthesized. A combined pH-metric and spectroscopic UV-VIS, EPR, CD and NMR study of Ni(II) and Cu(II) binding to the blocked hexapeptide, revealed the formation of octahedral complexes involving imidazole nitrogen of histidine, at pH 5 and pH 7 for Cu(II) and Ni(II) ions respectively. In basic solutions a major square-planar 4 N Ni(II)-complex, adopting a {N(Im), 3N(-)} coordination mode, was formed. In the case of Cu(II) ions, a 3 N complex, involving the imidazole nitrogen of histidine and two deprotonated amide nitrogens of the backbone of the peptide, at pH 7 and a series of 4 N complexes starting at pH 6.5, were suggested. In addition Ni(II)-mediated hydrolysis of the peptide bond-Tyr-Thr was evident following our experimental data.     

A Novel Dual Organocatalyst for the Asymmetric Pinder Reaction and a Mechanistic Proposal Consistent with the Isoinversion Effect Thereof

In general, the Pinder reaction concerns the reaction between an enolisable anhydride and an aldehyde proceeding initially through a Knoevenagel reaction followed by the ring closing process generating lactones with at least two chiral centers. These scaffolds are frequently present in natural products and synthetic bioactive molecules, hence it has attracted intense interest in organic synthesis and medicinal chemistry, particularly with respect to controlling the diastereo- and enantioselectivity. To the best of our knowledge, there has been only one attempt prior to this work towards the development of a catalytic enantioselective Pinder reaction. In our approach, we designed, synthesized, and tested dual chiral organocatalysts by combining BIMAH amines, (2-(α-(alkyl)methanamine)-1H-benzimidazoles, and a Lewis acid motif, such as squaramides, ureas and thioureas. The optimum catalyst was the derivative of isopropyl BIMAH bearing a bis(3,5-trifluoromethyl) thiourea, which afforded the Pinder products from various aromatic aldehydes with diastereomeric ratio >98:2 and enatioselectivity up to 92 ee%. Interestingly, the enantioselectivity of this catalyzed process is increased at higher concentrations and exhibits an isoinversion effect, namely an inverted "U" shaped dependency with respect to the temperature. Mechanistically, these features, point to a transition state involving an entropy-favored heterodimer interaction between a catalyst/anhydride and a catalyst/aldehyde complex when all other processes leading to this are much faster in comparison above the isoinversion temperature.     

Amino cyclodextrin per-O-methylation: Synthesis of 3-monoamino-permethylated derivatives

A method for the per-O-methylation of amino-cyclodextrins is described. The tert-butyloxycarbonyl protecting group was used for protection of the amino group since it is stable to the alkaline conditions necessary for the permethylation step and can be removed under mildly acidic conditions that leave the cyclodextrin skeleton intact. 3-Monoamino-α-permethylated cyclodextrin and 3-monoamino-β-permethylated cyclodextrin were synthesized based on the above method.     

Organocatalysis of asymmetric epoxidation by iminium salts using sodium hypochlorite as the stoichiometric oxidant

Iminium salts can provide high selectivity and high efficiency when used as organocatalysts for asymmetric epoxidation. For this purpose, they are normally used in conjunction with Oxone as the stoichiometric oxidant. Oxone, however, has limited stability, is insoluble in most organic solvents, is atom-inefficient, and produces considerable inorganic residue as the by-product of oxidation. In this paper we report for the first time the development of a reaction system driven by sodium hypochlorite as the stoichiometric oxidant.     

The Reaction of Diethylthiophosphinyl Iodide,Et2P(S)I,with Nucleophiles

The compound Me₂AsSI can exist in two different forms, either as dimethylarsinosulfenyl iodide [or (iodothio)dimethylarsane)], Me₂As–S–I ( A ), or as dimethylthioarsinyl iodide (or dimethylarsinothioic iodide), Me₂As(S)–I ( B ). To confirm that the structure of the product of the reaction between Bunsen's cacodyl disulfide Me₂As(S)–S–AsMe₂ and iodine is A and not B , the known diethylthiophosphinyl iodide (or diethylphosphinothioic iodide), Et₂P(S)–I ( 2 ) was prepared and its hydrolytic stability and reactivity towards a variety of nitrogen, phosphorus(III), arsenic(III), oxygen, and sulfur(II) nucleophiles were studied. The results indicated that only a few reactions of 2 resembled those of A , thus strengthening the proposal that the reaction of Bunsen's cacodyl disulfide with iodine produced A and not B . A series of ³¹P NMR chemical shifts of diethylthiophosphinyl moiety is also reported. Et₂P(S)–DMAP, synthesized and isolated during the presented study, is the ethyl analogue of Me₂P(S)–DMAP, previously described as an important molecule. In our case, Et₂P(S)–DMAP was found to be a good intermediate for the synthesis of phosphoryl or thiophosphoryl derivatives since it was more reactive than 2 towards nucleophiles.