Synthesis and evaluation of a bifunctional chelate for development of Bi(III)-labeled radioimmunoconjugates.

A new bifunctional ligand C-DEPA was designed and synthesized as a component for antibody-targeted radiation therapy (radioimmunotherapy, RIT) of cancer. C-DEPA was conjugated to a tumor targeting antibody, trastuzumab, and the corresponding C-DEPA-trastuzumab conjugate was evaluated for radiolabeling kinetics with (205/6)Bi. C-DEPA-trastuzumab conjugate rapidly bound (205/6)Bi, and (205/6)Bi-C-DEPA-trastuzumab conjugate was stable in human serum for 72 h. The in vitro radiolabeling kinetics and serum stability data suggest that C-DEPA is a potential chelate for preclinical RIT applications using (212)Bi and (213)Bi.

Efficient synthesis of functionalized aziridinium salts.

Various aziridinium salts were efficiently prepared from bromination of a series of backbone substituted N,N-bisubstituted beta-amino alcohols and isolated via flash column chromatography. The effect of C-substitution, N-substitution, solvent, leaving group, and counteranions on formation of the isolable aziridinium salts was investigated.

Rauhut-Currier type homo- and heterocouplings involving nitroalkenes and nitrodienes.

Reaction of nitroalkenes or nitrodienes with methyl vinyl ketone (MVK) or acrylate in the presence of the imidazole-LiCl catalyst system provides Rauhut-Currier (vinylogous Morita-Baylis-Hillman) adducts in moderate yield. Under similar conditions (imidazole-hydroquinone), nitroalkenes and nitrodienes undergo self-dimerization to afford the Rauhut-Currier adducts in varying yields. An alternative self-dimerization-nitro group elimination pathway in the presence tricyclohexylphosphine was observed with heteroaromatic nitroalkenes. A synthetically useful one-pot two step transformation of Rauhut-Currier adducts of nitroalkenes with MVK to 2,3-disubstituted cyclopentenones is also described.

Stable aziridinium salts as versatile intermediates: isolation and regio- and stereoselective ring-opening and rearrangement.

Rock trapping and exploration: Aziridinium bromide salts were discovered serendipitously during bromination of N,N-dicarboxymethylated beta-amino alcohols. Regiospecific ring-opening and rearrangement of the isolated, surprisingly stable aziridinium salts produces useful molecules including C-functionalized oxomorpholines and alpha,beta-unsaturated amines.

Hydroxyalkylation of conjugated nitroalkenes with activated nonenolizable carbonyl compounds.

[reaction: see text] The Morita-Baylis-Hillman reaction of a variety of conjugated nitroalkenes with activated nonenolizable carbonyl compounds such as glyoxylate, trifluoropyruvate, pyruvaldehyde, and ninhydrin in the presence of 40-100 mol % of DMAP in acetonitrile or 100 mol % of imidazole in CHCl(3) or THF provided the adducts in decent to good yields. In most cases, the reactions catalyzed by DMAP in acetonitrile were faster and provided the desired MBH adducts in higher yields as compared to the imidazole catalyzed reactions.

The Morita-Baylis-Hillman adducts of beta-aryl nitroethylenes with other activated alkenes: synthesis and anticancer activity studies.

The Morita-Baylis-Hillman (MBH) adducts of beta-aryl nitroethylenes with methyl vinyl ketone (MVK) and acrylate, formed in moderate to good yield when mediated by imidazole/LiCl in THF at room temperature, inhibit HeLa cell proliferation by binding to tubulin.

A highly effective bifunctional ligand for radioimmunotherapy applications.

A novel bifunctional ligand (3p-C-NETA) for antibody-targeted radioimmunotherapy (RIT) of ß-emitting radioisotopes (90)Y and (177)Lu was efficiently synthesized via an unexpected regiospecific ring opening of an aziridinium ion. 3p-C-NETA instantly formed a very stable complex with (90)Y or (177)Lu. 3p-C-NETA is an excellent bifunctional ligand for RIT.

Highly efficient hydrazination of conjugated nitroalkenes via imidazole or DMAP mediated Morita-Baylis-Hillman reaction.

Novel alpha-hydrazino-alpha,beta-unsaturated nitroalkenes, which exhibit dynamic phenomenon on the NMR time scale, were synthesized in excellent yields via imidazole or DMAP mediated Morita-Baylis-Hillman (MBH) type reaction of nitroalkenes with azodicarboxylates.