Michael Harmata

Control Elements in Dynamically Determined Selectivity on a Bifurcating Surface

The mechanism and the nature of the dynamically determined product selectivity in Diels-Alder cycloadditions of 3-methoxycarbonylcyclopentadienone (2) with 1,3-dienes was studied by a combination of product studies, experimental kinetic isotope effects, standard theoretical calculations, and quasiclassical trajectory calculations. The low-energy transition structures in these reactions are structurally balanced between [4pi(diene) + 2pi(dienone)] and the [2pi(diene) + 4pi(dienone)] modes of cycloaddition. The accuracy of these structures and their bispericyclic nature is supported by the experimental isotope effects. Trajectories passing through these transition structures can lead to both [4pi(diene) + 2pi(dienone)] and [2pi(diene) + 4pi(dienone)] cycloadducts, and the mixture of products obtained varies with the structure of the diene. The factors affecting this selectivity are analyzed. The geometry of the transition structure is a useful predictor of the major product, but the selectivity is also guided by the shape of the energy surface as trajectories approach the products and by how trajectories cross the transition state ridge.

Studies on DNA - active agents: The synthesis of the parent carbocyclic subunit of neocarzinostatin chromophore A

Abstract A synthesis of the parent carbocyclic subunit of NCS Chrom A ( 1 ) is described which provides corroborative support for the assigned but unprecedented structure of the active subunit of 1 , reference data for future synthetic and mechanism of action studies, and a general strategy for analogue and total synthesis.

Congeners of Troeger's base as chiral ligands

Abstract ( S )-(+)-Troegers base can be deprotonated and alkylated without loss of stereochemical integrity. An examination of the ability of Troegers base and several derivatives prepared in this fashion to effect asymmetric induction in the addition of diethylzinc to aromatic aldehydes was conducted. Enantiomeric excesses as high as 86% were achieved, providing evidence that Troegers base represents a chiral framework which can be modified to produce ligands for catalytic asymmetric synthesis.

A ONE-POT, ONE-OPERATION 3+3 ANNULATION APPROACH TO BENZOTHIAZINES

Enantiomerically pure 2,1-benzothiazines are readily prepared by a one-pot, one-operation procedure consisting of a palladium-catalyzed aryl amination of an ortho-bromobenzaldehyde with a sulfoximine followed by an intramolecular condensation reaction [Eq. (1)]. BINAP=1,1′-binaphthalene-2,2′-diylbis(diphenylphosphane).

Origin of stereoselectivity in the (4 + 3) cycloadditions of chiral alkoxy siloxyallyl cations with furan

The mechanisms and stereoselectivities of (4 + 3) cycloadditions between chiral alkoxy siloxyallyl cations and furan are examined using density functional theory calculations. These cycloadditions are predicted to take place via stepwise mechanisms. The stereoselectivities of cycloadditions involving siloxyallyl cations derived from chiral alpha-methyl benzylic alcohols are controlled by two effects: minimization of steric repulsion between the alpha-Me group and the allyl group and attractive CH-pi interactions between the furan and the aryl group.

Benzothiazines in synthesis. Formal syntheses of (+)-curcumene and (+)-curcuphenol

A benzothiazine readily available in enantiomerically pure form via a stereoselective, intramolecular Michael addition reaction could be converted to a precursor to (+)-curcuphenol and to (+)-curcumene.

Intramolecular 4+3 cycloadditions. Vinylthionium ions from allylic alcohols

Abstract Aldehyde 9 can be prepared from ethyl pyruvate in several steps. Treatment of 1 with various diene-containing Grignard reagents results in the formation of the corresponding allylic alcohol in good yield. Exposure of these alcohols to triflic anhydride results in the formation of 4+3 cycloadducts in good to excellent yields. Furan and simple butadiene trap the intermediate allylic cation efficiently in the formation of 5,7-fused ring systems. A tethered thiophene undergoes only intramolecular Friedal-Crafts alkylation.

Purification and characterization of a Coffea canephora α-D-galactosidase isozyme

Abstract Exoglycosidases modify carbohydrate epitopes on glycoproteins and glycolipids. The α-D-galactosidase from Coffea canephora is an important exoglycosidase which degrades the human blood group B epitope. Although multiple isozymes have been described, they have never been demonstrably purified and thoroughly characterized. We have developed a technique to purify an isozyme to homogeneity. The isolated enzyme has a molecular weight of 36.7 kDa by SDS PAGE and 34.0 kDa by gel filtration. The isozyme is highly selective for α-D-galactosides and inactive against other low molecular weight substrates. It hydrolyzes the the terminal α-D-galactosyl residue from the blood group B epitope. Protease activity is below detectable limits. The isozyme has a broad pH optima at 6.3, a pl of 7.03, is unaffected by ionic strength, and is stable at 4° C.

The metallation of Troeger's base

Abstract Complexation of Troegers base with boron trifluoride etherate followed by treatment with n-BuLi results in the formation of an anion. This reacts with electrophiles stereoselectively to give alkylation products in good to excellent yields.

The determination of the absolute configuration of a chiral molecular tweezer using CD spectroscopy

Abstract Calculation of the CD spectrum of 1 and comparison to an experimentally determined CD spectrum is used to establish the absolute stereochemistry of 1 .