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A study was conducted to characterize a way to monitor a reaction sequence on resin. Magic angle spinning nuclear magnetic resonance (NMR) and Fourier transform infrared were used for the nondestructive monitoring process. The identity of acrylate was determined using 13C NMR while alkylation was carried out to form the tetrasubstituted amine salt with allylic bromide. Results indicated that the combination of techniques can effectively support the nondestructive testing of resins.

Research was conducted to investigate the application of the Hofmann elimination of tetrasubsituted amine salts on solid-phase resin to produce diverse combinatorial libraries of trisubstituted amines. The diversity of disubstituted amines, cyclic and noncyclic was examined as a second step of alkylation while quaternary ammonium compounds were bound by overnight agitation. Results showed the success of amberlite-promoted Hofmann eliminations in solution-phase organic syntheses.

Investigations into the Ugi five-component condensation (5CC), which allows the synthesis of carbamate-protected aminoamide, aminothioamide and thiourea-thioamide core structures in a single reaction, were conducted. The 5CC is the condensation of an amine, a carbonyl compound, an alcohol, an isocyanide and carbon dioxide to produce an alpha-(alkoxylcarbonylamino)amide. Results demonstrate that the yields of product range from poor to very good and reveal that methanol is clearly the superior alcohol substrate.

A novel method for the synthesis of 1,4-benzodiazepine-2,5-diones (BZDs) was developed based on an Ugi four-component condensation mediated by isocyanide(1-isocyanocyclohexene). The novel two-step procedure for the synthesis of diverse 1,4-benzodiazepine-2,5-diones takes advantage of the maximal input diversity offered by the Ugi four-component condensation. Furthermore, the synthetic process is characterized by the conformational isomerization of the BZD skeleton and slow alkyl substitution.

The Ugi reaction was used in synthesizing diverse 1,4-benzodiaepine-2,5-diones (BZDs) 1 to derive the precursor alpha-acylaminoamide 3. The Ugi four-component condensation is also considered for a diverse compound class using a convertible isocyanide. The method improves initial BZD tests and offers greater potential for molecular diversity.

The solid phase Ugi four-component condensation with various functionalized C-glycosides which can utilize different protecting group techniques is used to demonstrate the solid phase synthesis of glycomimetic candidiates which structurally resemble cell surface carbohydrates. It is touted as a simple yet highly efficient method for attaining rapid diversity in libraries focusing on carbohydrate receptor ligands. It is demonstrated through the synthesis of eight monosaccharides and disaccharides and a 96-well, 192-compound library of glycomimetics targeting the receptors of sialyl Lewis x.

Synthesis of hapalosin by chelation-controlled reduction of a gamma-amino-beta-keto-ester and cycloamidation revealed the synthetic hapalosin as a 2:3:1 mixture of conformers while its non-N-Me analog exists as a single conformer. Their conformations are determined by the configuration of the amide bond. The major conformer has an s-cis amide bond while the minor conformer as well as the non-N-Me analog have s-trans amide bonds. The major conformer of hapalosin and the non-N-Me analog have vastly different conformations. On the other hand, the minor conformer and the non-N-Me analog have very similar conformations.

Synthesis of the C1-C25 spiroketal core fragment of calyculin C was conducted based on an allylboration strategy. The process focused on the initial disconnection of the C25-C26 double bonds which leads to the formation of a product with two similar functional density. The desired stereochemistry was acquired by the initial synthesis of the C21-C25 spiroketal core and its subsequent homologation based on chiral allylboration strategy.

A functionalized C26-C37 oxazole fragment was synthesized based on a stereospecific method that utilizes an amino acid-based strategy. The method was based on the disconnection of the C33-N3 amide bond for the efficient use of C33-C37 aza-sugar fragment and the C26-C32 fragment. The synthesis of enantiomeric C33-C37 fragments depends on the abundant supply of aldopentoses and requires a double inversion at the C4 of D-ribose. The production of the C26-C37 fragment was based on the identification of the proper sequence of phosphonium salt formation and debenzylation.

The present route for the synthesis of tautomycin allows isotopic labeling and minor structural modification. The spiroketal compound, incorporating the C-1 to C-21 fragment of tautomycin, is synthesized from methaneboric acid. Stereocenters at C-3 and C-13 to C-21 are put up in the spirocyclic half of tautomycin by Matteson's stereospecific insertion of chloromethylene into a boron-carbon bond as guided by the pinanediol chiral auxiliary. The two spirocyclic halves undergo coupling in the presence of Cr/Ni and generate a structure with the C-1 to C-21 portion of tautomycin.

Key precursors for the production of extremely functionalized dehydroamino acid derivatives, upon condensation with glycyl phosphonates, resulted from the preparation of aldehydes from D-arabinose. The azabicyclo (3.1.0) hex-2-ylidine ring systems believed to be present in the azinothycin antitumor antibiotics, resulted from brominatin and intramolecular addition/elimination.

The (E)- and (Z)-1-azabicyclo(3.1.0)hex-2-ylidine dehydroamino acid compounds can be prepared from the bromination of dehydroamino acids followed by cyclization of the olefinic beta-bromodehydroamino acid derivatives. The bromination process involves the introduction of either N-bromosuccinimide or Br2/2,6-lutidine which promotes the formation of vinyl bromides with high diastereoselectivity. Moreover, an intramolecular Michael addition-elimination with retention of olefin configuration characterizes the cyclization process which eventually forms 1-azabicyclo(3.1.0)hex-2-ylidine ring structures that correspond to azinomycin antibiotics.

A stereoselective route to beta-disaccharides with methylene in place of oxygen links involves bromine-catalyzed 6-endo-trig cyclization of D-arabinose-derived E olefins. This method is used to prepare alpha-methyl 1',2'- dideoxycellobioside. The use of trans-actonide olefins prevents furan formationdue to restricted rotation about the glycosidic bond. Stereocenters at the exo-anomeric carbon, which is prevented from taking part in the cyclization, are thus stabilized. This allows a unique staggered conformation for the disaccharide.

A mild procedure for preparing spiro alpha-hydroxy S-methylisothioureas from cyclic ketones is discussed. It involves the derivation of 2-thiohydantoin 4-imine via an Ugi four-component condensation using benzyl isocyanide followed by the reduction of the 4-imine with sodium cyanoborohydride and iodine in methylene choride and tetrahydrofuran. The latter affords an alpha-benzylamino thiourea which may be converted into an alpha-hydroxy thiourea. Meanwhile, modification of the process yields alpha-hydroxy S-methylisothiourea.

Solid support via resin capture method was used to synthesize the estrogen antagonist tamoxifen and its derivatives. Isolation of the resin was done by filtration and purified by washing. Results show that these derivative forming reactions are dependent on resin capture and a silicon linker. Modification of each position about the ethylene core can be done using resin capture with the appropriate choice of alkyne, aryl halide and cleavage conditions.

An alternative method of synthesizing benzofuran derivatives was designed through SmI2-mediated aryl radical cyclizations on solid support. The design featured the utilization of polyethylene glycol-grafted resins as coupling medium. NMR spectra of the crude products have shown the predominance of cyclized products with a small percentage of the reduced products. Reduction of the aryl iodide was a minor side reaction.

The synthesis of the four proline analogs of the cyclic depsipeptide hapalosin is described. The anti-multidrug resistance properties of the synthetic hapalosin and its analogs were determined by cytotoxicity and drug accumulation assays using MNC-7/ADR cells. The results showed the importance of a free hydroxyl and an aromatic group in the anti-MDR activities of the compounds.

The acid chloride coupling method was employed to synthesize hapalosin, a cyclic depsipeptide which can contravene P-glycoprotein-mediated multidrug resistance in vitro. The procedure, which produced a 13% yield of hapalosin, involved the coupling of a synthetic amino alcohol and ester acid, the macrolactonization of a hydroxyacid under Mukaiyama conditions, and deprotection of the TBS ether of the macrolide.

Presents an extension of the approach developed for the synthesis of 12 C-trisaccharide glycomimetics of the H type I blood group determinant having a general structure which possesses a diverse core hexose. Study methodology; Description of the generation of 11 C-trisaccharides having the formula Fuc-C-(1-2)-hexose-C-(1-x)-GlcNAc; Findings of study; Discussion and conclusion to the results.

Presents a mild synthetic route for building spiro alpha-hydroxy S-methylisothioureas from cyclic ketones. Discussions on the mechanism of reduction; Accessibility of masked spirohydroxyguanidine; Usefulness for the synthesis of spiroguanidines in the presence of functional groups.

Describes the total synthesis of hapalosin, a multidrug resistance-reversing agent. Incorporation of a Passerini reaction; Synthesization of hapalosin using the acid chloride coupling method; Synthesization of amino alcohol in four steps.

We report our synthesis of the C(26)-C(37) fragment of serine/threonine protein phosphatase PP1 and PP2A inhibitor calyculin C (1). Outlined in this paper are synthetic approaches to the two components based on disconnection at the C(33)-N(3) amide bond. We report the successful synthesis of the C(33)-C(37) aza-sugar derived from D-lyxose which was coupled onto a C(26)-C(32) aminooxazole originating from L-pyroglutamic acid. Elaboration of the resulting amide to a fully deprotected C(26)-C(37) fragment of calyculin C completed our synthesis. This provided an appropriate phosphonium salt for use in a Wittig olefination for joining both halves of the natural product.

We report our synthesis of the C(1)-C(25) fragment of serine/threonine phosphatase PP1 and PP2A inhibitor, calyculin C. Synthetic efforts were directed initially toward the synthesis of a spiroketal core fragment (7), which culminated in completion of the bottom half of the natural product. The synthesis of fragment 7 and subsequent elaboration relied on an allylboration strategy for introduction of chirality. The C(1)-C(8) fragment representing the potentially unstable tetraene moiety was introduced as a separate entity.