Search

An analysis of the total synthesis of calyculin C showed that the diastereoselectivity characterizing C10-C11-propionate stereocenters exhibited a remote protecting group effect. This effect was observed for the serine/threonine phosphatase inhibitor's C1-C25 fragment. Other synthesis results include the development of C25-C26 double bond through a deprotected C26-C37 phosphonium salt and confirmation of stereochemistry at C34.

The use of 1-isocyanocyclohexene as an 'universal isocyanide' input in the Ugi one-pot condensation enables the postcondensation conversion of its Ugi four-component product, alpha-(acylamino) amides such as cyclohexenamide, into a variety of functionalities. These include carboxylic acids, esters, thioesters, pyrroles, sugars and 1,4-benzodiazepine-2,5-diones. The trapping Ugi products of a solution reaction onto a solid support resin is also carried out.

The squaric acid derived synthesis of fused aromatic and heteroaromatic cores was identified as a reaction platform for the generation of MCSLs. The first route involved a halogenated aryl ether on Wang resin, generated through the Mitsunobu reaction, coupled with tributyltin isopropyl squarate under Stille conditions. The second route avoided the synthesis of the stannylated squarate.

A general approach for the synthesis of C-trisaccharides bearing 1,2 sugar branching was developed using the H type I blood group determinant. Two pendant sugars were attached to the terminus of the trisaccharide. A central hexose core was created for the C-trisaccharide and permutational mutations to these core caused changes to the trisaccharide's overall conformation. The steps to the synthesis of more trisaccharides bearing a variety of structures are discussed.

Tetrasubstituted ethylenes may be synthesized on a solid support by means of resin capture. Platinum-catalyzed diboration of alkynes yields bis(boryl)alkenes. The bis(boryl)alkenes are then monoalkylated in a solution Suzuki reaction with halide substrates, then reacted in the same manner again with a resin-bound halide. A library may thus be generated of alkyl, benzyl, allyl, vinyl and aryl halides and stored on resin.

A new combinatorial library method involving radio frequency encodable microchip with a polypropylene capsule of derivatized polystyrene suitably identifies novel protein tripeptide-substituted cinnamic acid inhibitors of protein tyrosine phosphatase. A tripeptide amide acetylated at the N-terminus is used as the library substrate. The library reveals glutamate residues in most potent inhibitors however CinnGEL and CinnGEE lack this position. Electron density maps of protein surface reveal an aggregate of positively charged clusters.

Carzinophilin is an antitumor antibiotic which is found to cause significant DNA damage due to cross-link formation. It is discovered that bifunctional alkylation of carzinophilincauses interstrand cross-links in the major groove between G and certain purine residues. This is shown by the rational design of synthetic oligonucleotides containing the bases inosine and 7-deazaguanine at the target alkylation sites.

The successful stereoselective synthesis of 1-azabicyclo(3.1.0)hex-2-ylidene acetophenone provides a potential route to thepractical synthesis of azinomycins. Azinomycins are potent anti-leukemia drugs presently extracted from Streptomyces griseofuscus. The active component of azinomycin is the dehydroamino acid containing the 1-azabicyclo(3.1.0)hex-2-ylidene ring system. The key step in the synthesis is the intramolecular cyclization of aziridine, accomplished through addition of triethylamine at 50 degC. The yield is 75% Z isomer.

Research was conducted to examine the total synthesis of motuporin. The objective was to analyze the varied functionality of the molecule as well as to gain an insight into the synthesis of a number of inhibitors in the nodularin class. It was hypothesized that in the corresponding pentapeptide structure, the residue should also be in the active site and hence would be a good choice for modification and analogue studies.