Abstract: A process for catalyzing asymmetric dihydroxylations of olefins employs an Os(VI) complex as a catalytic intermediate in the formation of chiral vicinal diol products. The process requires a chiral bidentate ligand that favors diol formation in the “second cycle” of asymmetric dihydroxylation.

Abstract: A reaction cassette has been designed for the highly sensitive detection of the making and breaking of chemical bonds. The system may be employed as a companion device to be used in the search for antibody and other novel catalysts. The cassette also has important clinical applications in the design of diagnostic reagents. In its fully encoded format this methodology is capable of both detecting and decoding chemical events.

Abstract: With the help of X-ray structural analyses of drug-resistant HIV proteases and molecular modeling, a new type of inhibitor with a small P3 residue has been developed. These inhibitors are effective against HIV and its drug-resistant mutants, as well as FIV. Modification of existing HIV protease inhibitors effective against the wild type and drug-resistant mutants and further supports that FIV protease is a useful model for drug-resistant HIV proteases, which often are developed through reduction in size of the binging region for the P3 group or the combined P3 and P1 groups.

Abstract: Designed iminocylitols that have potent inhibition activity with respect to hexominidases and glycosides are disclosed.

Abstract: Analogs related to oleamide are employed for potentiating the 5-HT2A and 5-HT1A responses to serotonin (5-HT). With respect to the potentiation of the 5-HT2A receptor response, it is disclosed that, of the naturally occurring fatty acids, the primary amide of oleic acid (oleamide) is the most effective potentiating agent of serotonin and that the potentiating activity of oleamide analogs is highly dependent upon their structural features. In particular, the presence, position, and stereochemistry of the 9-cis double bond is required and even subtle structural variations reduce or eliminate activity. Secondary or tertiary amides may replace the primary amide but follow a well-defined relationship requiring small amide substituents suggesting that the carboxamide serves as a hydrogen bond acceptor but not donor. Alternative modifications at the carboxamide as well as modifications of the methyl terminus or the hydrocarbon region spanning the carboxamide and double bond typically eliminate activity.

Abstract: Peptidomimetic azatides and combinatorial oligoazitide libraries are produced by means of a stepwise synthesis. Combinatorial library construction of this new biomimetic polymer provides a means to fabricate global peptidomimetic libraries.

Abstract: Epothilone A, epothilone B, analogs of epothilone and libraries of epothilone analogs are synthesized. Epothilone A and B are known anticancers agents that derive their anticancer activity by the prevention of mitosis through the induction and stabilization of microtubule assembly. The analogs of epothilone are novel. Several of the analogs are demonstrated to have a superior cytotoxic activity as compared to epothilone A or epothilone B as demonstrated by their enhanced ability to induce the polymerization and stabilization of microtubules.

Abstract: Targeted C2-symmetric and unsymmetric chemical libraries for use in protein and receptor homodimerization and heterodimerization are constructed by solution phase methodologies. Exemplary libraries are prepared in a 60 to 10 sub-library format by symmetrical coupling of the constructed fragments with a mixture of tethering dicarboxylic acids. In each step of the 3-step reaction sequence, the reactants, unreacted starting material, reagents and their byproducts were removed by simple liquid-liquid or liquid-solid extractions providing the desired intermediates and final libraries in multi-milligram quantities in high purities (≧90-100%) independent of the reaction yields and without deliberate reaction optimization. The synthesis of a second prototypical library employed the olefin metathesis reaction to join and combinatorially randomize the length of linker tether.

Abstract: &bgr;-keto esters are prepared by way of a lipase-catalyzed transesterification. The synthetic methodology provides a simple scheme for the synthesis of optically active &bgr;-keto esters that are useful building blocks and starting materials for natural product synthesis. Moreover, the methodology employs mild, solvent-free conditions. The methodology may also be employed for resolving racemic alcohols.

Abstract: Modified proteins are represented by the formula R-L-R′, wherein R and R′ are peptides or pseudopeptides linked to one another by linkage L. Linkage L may be either a thiol ester pseudopeptide backbone linkage or a selenol ester pseudopeptide backbone linkage.

Abstract: Cyclic homodetic peptides having a repeating D-L-chirality motif are shown to have a stable disk conformation with the amino acid side chains extending radially outward and the carbonyl and amino groups extending axially upward or downward. Such cyclic peptides can be employed as subunits in the assembly of molecular tubes. Cyclic peptides having a repeating D-L-chirality motif and lacking mutually repulsive side-chains are shown to stack atop one another in an anti-parallel fashion and are shown to be held together by the formation of &bgr;-sheet hydrogen bonding. The stacked cyclic peptides form a molecular tube having a central channel. The diameter of the channel is determined by the size cyclic peptide. If the cyclic peptide includes ionizable amino acid residues, e.g. glutamic acid or lysine, assembly and disassembly of the molecular tubes can be controlled by varying the pH. If the cyclic peptide includes hydrophobic amino acid residues, the molecular tube will insert into a lipid membrane.

Abstract: &agr;,&bgr;-Unsaturated amides and esters are converted to &agr;,&bgr;-substituted amino amides, esters, and acids. An &agr;,&bgr;unsaturated amide or ester is first converted to an &agr;,&bgr;-hydroxysulfonamide or hydroxycarbamate amide or ester using an osmium-catalyzed aminohydroxylation. The &agr;,&bgr;-hydroxysulfonamide or hydroxycarbamate amides or esters is then cyclodehydrated to produce a &agr;,&bgr;-N-sulfonyl- or the &agr;,&bgr;-N-carbamoylaziridine amide or ester. The ring of aziridine intermediate is then nucleophilically opened in a regioselective manner with a variety of nucleophiles to give the $g(&agr;,&bgr;-substituted amino- amides or esters. Preferred nucleophiles include sulfur, oxygen, carbon, and nitrogen nucleophiles.

Abstract: Analogs of the antitumor antibiotics CC-1065 and the duocarmycins incorporate the 1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-one (CBI) alkylation subunit. The CBI-based analogs have potent cytotoxic activity and are useful as efficacious antitumor compounds. A direct relationship between functional stability and in vitro cytotoxic potency is disclosed. The CBI-based analogs are easily synthesized and are 4× more stable and 4× more potent than the corresponding analogs containing the authentic CPI alkylation subunit of CC-1065 and comparable in potency to agents containing the authentic alkylation subunit of duocarmycin SA. Similarly, the CBI-based agents alkylate DNA with an unaltered sequence selectivity at an enhanced rate and with a greater efficiency than the corresponding CPI analog and were comparable to the corresponding analog incorporating the duocarmycin SA alkylation subunit.

Abstract: D-enzyme compositions are described comprising an amino acid residue sequence that defines an polypeptide able to catalyze an enzymatic reaction. The D-enzyme has an amino acid residue sequence consisting of D-amino acids and glycine.

Abstract: The reactivity of a number of p-methylphenyl thioglycoside (STol) donors which are either fully protected or have one hydroxyl group exposed has been quantitatively determined by HPLC in conjunction with the development of a broadly applicable approach for a facile one-pot synthesis of oligosaccharides. The influence on reactivity of the structural effects of different monosaccharide cores and different protecting groups on each glycoside donor is characterized and quantified. In addition, a correlation between glycosyl donor reactivity and the chemical shift of the anomeric proton by 1H NMR has been established. A database of thioglycosides as glycosyl donors has been created using this reactivity data. The utility is demonstrated by the easy and rapid one-pot assembly of various linear and branched oligosaccharide structures.

Abstract: The invention relates to epothilone analog represented by formula (I) wherein (i) R2 is absent or oxygen; “a” can be either a single or double bond; “b” can be either absent or a single bond; and “c” can be either absent or a single bond, with the proviso that if R2 is oxygen then “b” and “c” are both a single bond and “a” is a single bond; if R2 is absent then “b” and “c” are absent and “a” is a double bond; and if “a” is a double bond, then R2, “b” and “c” are absent; R3 is a radical selected from the group consisting of hydrogen; lower alkyl; —CH═CH2; —C≡CH; —CH2F; —CH2Cl; —CH2—OH; —CH2—O—(C1-C6-alkyl); and —CH2—S—(C1-C6-alkyl); R4 and R5 are independently selected from hydrogen, methyl or a protecting group; and R1 is as defined in the specification, or a salt of a compound of formu

Abstract: Phosphite linked nucleotide sugars, e.g. nucleoside-monophosphite-glycosides, are synthesized using phosphoramiditing agents. The success of the synthetic method is largely independent of the choice of sugar and of nucleotide. The phosphite linked nucleotide sugars are shown to be useful, in the presence of an oxidizing agent, for the production of phosphate linked nucleotide sugars, e.g. nucleoside-monophosphate-glycosides.

Abstract: D- and L- &agr;-amino acids and D- and L-&agr;-amino aldehydes are synthesized from olefin substrates in two steps. The first step is a catalyzed asymmetric aminohydroxylation addition reaction to the olefin substrate. The addition reaction is catalyzed by osmium and is co-catalyzed by chiral ligands. The chiral ligands, in addition to being co-catalysts with the osmium, also serve to direct the addition reaction regioselectively and enantioselectively, divalent ligands are preferred over monovalent ligands because of their enhanced regio-and enantio-selectivity. As an oxidant nitrogen source for the addition reaction, either a carbamate or sulfonamide may be employed. If carbamate is employed as an oxidant nitrogen source, the resultant &bgr;-hydoxycarbamate is deprotected to yield the corresponding &bgr;-hydroxyamine. If sulfonamide is employed as an oxidant nitrogen source, the resultant &bgr;-hydroxysulfonamide is deprotected to yield the corresponding &bgr;-hydroxyamine.

Abstract: A protein signature analysis is obtained using a peptide ladder library. The molecular signature of a protein is defined to be that subsequence of amino acid positions within the protein which are essential for the protein to bind to a target molecule. The molecular signature may be determined by screening a peptide ladder library which corresponds to the protein against the target molecule. The peptide ladder library is a library of m peptides wherein each peptide has an amino acid sequence of length m corresponding to an amino acid sequence of the protein, with one exception, viz. peptidem has a substitute amino acid at positionm and the substitute amino acid is attached by a labile bond to its neighboring amino acid. Screening the peptide ladder library against the target molecule results in a division of the original mixture into a positive (functional) pool and a negative (non-functional) pool. The pools are separated and subjected to cleavage to obtain cleavage products.

Abstract: A series of bioactive analogs of (+)-CC-1065 (1) and the duocarmycins 2 and 3 are synthesized. The bioactive analogs include either iso-CI or iso-CBI (6 and 7) as a DNA alkylation subunit. Conjugated to the DNA alkylating subunits are a variety of DNA binding subunits. The bioactive analogs maintain their DNA selectivity and display enhance reactivity.