Convenient synthesis of N-methylamino acids compatible with Fmoc solid-phase peptide synthesis

N(alpha)-Methylamino acid containing peptides exhibit interesting therapeutic profiles and are increasingly recognized as potentially useful therapeutics. Unfortunately, their synthesis is hampered by the high price and unavaibility of many N(alpha)-methylamino acids. An efficient and practical preparation of N(alpha)-methyl-N(alpha)-(o-nitrobenzenesulfonyl)-alpha-amino acids without extensive purification is described. The procedure is based on the well-known N-alkylation of N(alpha)-arylsulfonylamino esters which was improved by using dimethyl sulfate and DBU as base. Ester cleavage is efficiently achieved by using an S(N)2-type saponification with lithium iodide, avoiding racemization observed with lithium hydroxide hydrolysis. Compatibility of the synthesized N(alpha)-methylamino acids with Fmoc solid-phase peptide synthesis is demonstrated by using normal coupling conditions to efficiently prepare N-methyl dipeptides. The described procedure allows the preparation of N(alpha)-methylamino acids in a very short period of time and a rapid synthesis of N-methyl peptides using Fmoc solid-phase peptide synthesis.     

Synthesis of an azacrown template for phosphatidylinositol-4,5-bis(phosphate) recognition

An azacrown system has been developed for selective membrane binding of phosphatidylinositol-4,5-bis(phosphate) recognition. Neutral and cationic forms of the metacyclophane macrocycles have been synthesized by divergent routes in acceptable yields. Such diversity will be useful in identifying anion receptors that operate best at membrane interfaces.     

Synthesis of the C(43)-C(67) fragment of amphidinol 3

[reaction: see text] A synthesis of the C(43)-C(67) fragment of amphidinol 3 (AM3) has been accomplished by a route that features the use of a double allylboration reaction for synthesis of 1,5-diol 4b, which serves as a precursor to dihydropyran 11.     

Mechanistic studies of nickel(II) alkyl agostic cations and alkyl ethylene complexes: investigations of chain propagation and isomerization in (alpha-diimine)Ni(II)-catalyzed ethylene polymerization

The synthesis of a series of (alpha-diimine)NiR(2) (R = Et, (n)Pr) complexes via Grignard alkylation of the corresponding (alpha-diimine)NiBr(2) precursors is presented. Protonation of these species by the oxonium acid [H(OEt(2))(2)](+)[BAr'(4)](-) at low temperatures yields cationic Ni(II) beta-agostic alkyl complexes which model relevant intermediates present in nickel-catalyzed olefin polymerization reactions. The highly dynamic nature of these agostic alkyl cations is quantitatively addressed using NMR line broadening techniques. Trapping of these complexes with ethylene provides cationic Ni alkyl ethylene species, which are used to determine rates of ethylene insertion into primary and secondary carbon centers. The Ni agostic alkyl cations are also trapped by CH(3)CN and Me(2)S to yield Ni(R)(L)(+) (L = CH(3)CN, Me(2)S) complexes, and the dynamic behavior of these species in the presence of varied [L] is discussed. The kinetic data obtained from these experiments are used to present an overall picture of the ethylene polymerization mechanism for (alpha-diimine)Ni catalysts, including effects of reaction temperature and ethylene pressure on catalyst activity, polyethylene branching, and polymer architecture. Detailed comparisons of these systems to the previously presented analogous palladium catalysts are made.     

Dendritic nanowire ultraviolet laser array

Self-organized dendritic crystal growth is explored to assemble uniform semiconductor nanowires into highly ordered one-dimensional microscale arrays that resemble comb structures. The individual ZnO nanowires have uniform diameters ranging from 10 to 300 nm. They are evenly spaced on a stem with a regular periodicity of 0.1-2 micrometer. Under optical excitation, each individual ZnO nanowire serves as a Fabry-Perot optical cavity, and together they form a highly ordered nanowire ultraviolet laser array.     

Copper(II) chloride complexes with multimodal ligands based on the cyclotriphosphazene platform

The reaction of hexakis(2-pyridyloxy)cyclotriphosphazene (L) and hexakis(4-methyl-2-pyridyloxy)cyclotriphosphazene (MeL) with copper(ii) chloride afford the complexes [CuLCl(2)], [(CuCl(2))(2)(MeL)], [CuLCl]PF(6) and [Cu(MeL)Cl]PF(6). The single-crystal X-ray structure of [CuLCl(2)] shows the copper ion to be in a square based pyramidal distorted trigonal bipyramidal (SBPDTBP) environment (tau= 0.47) with L acting as a kappa(3)N donor, coordinating via the nitrogen atoms from two non-geminal pyridyloxy pendant arms, a nitrogen atom in the phosphazene ring and two chloride ions. In the dimetallic complex, [(CuCl(2))(2)(MeL)], the geometry about both (symmetry related) copper(ii) centres is also SBPDTBP (tau= 0.57) with a 'N(3)Cl(2)' donor set. In the monocation of [CuLCl]PF(6), L acts as a kappa(5)N donor, bonding to the copper(ii) centre through the nitrogen atoms of four pyridyloxy pendant arms, a phosphazene ring nitrogen atom and a chloride ion to give an elongated rhombic octahedral coordination sphere. The phosphazene ring atoms remain virtually coplanar in all three structures as a consequence of the phenoxy-hinge, which links the pyridine pendant donors to the cyclotriphosphazene platform, allowing the formation of six-membered chelate rings. The spectroscopic (mass spectral, EPR and electronic) and magnetic properties of the complexes are discussed. The EPR and variable temperature magnetic susceptibility results for the dicopper complex, [(CuCl(2))(2)(MeL)], point to a very weak electronic interaction between the metal atoms.     

Student-Designed Multistep Synthesis Projects in Organic Chemistry

The incorporation of research projects into undergraduate chemistry courses provides a perspective that is fundamentally unavailable in most laboratory experiences. While independent, multistep synthesis projects in organic chemistry have been reported previously, most efforts have been directed at relatively restricted, closely guided research plans with modest student participation in the experimental design. We have implemented a more open-ended synthesis project, limited principally by cost, safety and availability of materials. In the second semester of the sophomore organic sequence, students develop multiple drafts of a plan for a three-to-four-step synthesis. Subsequently, students obtain their own literature protocols for the individual steps. The synthesis is performed over three four-hour laboratory periods. The students conclude this project with a poster presentation of the results at the end of the semester. Evaluation of the students work focuses not only on the successful synthesis of the target but also on planning, troubleshooting, purification, and spectral analysis.     

Some reactions of copper(I) pentafluorothiophenolate as a nucleophile

Several aromatic compounds containing one or two C₆F₅S groups have been prepared by nucleophilic displacement reactions using CuSC₆F₅ in DMF solution. Aromatic iodine or bromine, rather than chlorine of fluorine is replaced by the SC₆F₅ group using CuSC₆F₅. A mechanism is postulated. New compounds prepared include $\text{p}$-(C₆F₆F₅S)₂C₆H₄, $\text{o}$- and $\text{m}$-(C₆F₅S)₂C₆F₄ and $\text{p}$XC₆H₄SC₆F₅(X=C1, NO₂, I, CH₃, CO₂C₂H₅).     

Concise synthesis of anhydrovinblastine from leurosine

[reaction: see text] The Cp(2)TiCl-mediated deoxygenation of leurosine (1) afforded anhydrovinblastine (4) in good yield. Furthermore, as the reaction proceeded via a carbon-centered radical intermediate, this transient was also trapped by a hydrogen-atom donor to afford selectively reduced alkaloid 10.