Multi-step polymer-assisted solution-phase (PASP) library synthesis of functionalized diaminobenzamides.

A parallel solution-phase library synthesis of functionalized diaminobenzamides is described. The four-step library synthesis is accomplished using polymer-assisted solution-phase (PASP) synthesis techniques. This high-yielding, multi-step sequence utilizes sequestering resins for the removal of reactants, reactant by-products, and employs a resin capture/release strategy as a key library synthesis step. Step one of the sequence relies on the displacement of an activated fluoro-group from the aromatic ring of 1a, b with a variety of primary amines to introduce the first diversity position. Step two is hydrolysis of the benzoate ester to a benzoic acid which is subsequently captured on a polyamine resin, washed, and released to give 4a, b in pure form. Step three utilizes PASP resins to mediate the amide coupling of a benzoic acid with a variety of primary amines to give the aminonitrobenzamides 5a, b and introduces the second diversity position. Step four is the parallel reduction of the aminonitrobenzamides 5a, b to the functionalized diaminobenzamides 6a, b. This library synthesis proceeds with high overall purities which average 80 % over the 4-step sequence.

Fluorous-phase soluble polymeric supports.

Fluorous phase soluble polymer supports derived from fluoroacrylate polymers are described. N-Acryloxysuccinimide-containing fluoroacrylate polymers were readily prepared from commercially available monomers. The activated acrylates so prepared were then converted into chelating and non-chelating ligands by amidation of the N-acryloxysuccinimide active ester residues. Phosphine ligands attached to these supports were used to prepare neutral and cationic rhodium(I) hydrogenation catalysts as well as palladium(0) catalysts. Similar substitution of pendant active ester groups to form hydroxamic acid ligands for metal sequestration is also feasible. Liquid/liquid extraction readily separated, recycled and reused these polymer-bound ligands and catalysts. While fluorous phase solubility could be attained with polymers containing only heptafluorobutyryl groups, selective solubility in a fluorous phase in contact with an organic phase was only seen with fluoroacrylates that contained larger fluorinated ester groups.

Mitotic processes which restore genome balance in Aspergillus nidulans.

Previous work had shown that haploid strains of Aspergillus nidulans with a duplicate chromosome segment (one in normal position, one translocated to another chromosome) were unstable at mitosis; genome balance was restored by spontaneous deletion of either duplicate segment. Diploids with an extra, translocated segment showed high instability which was confined to the excess segments; loss of one of these, usually that in translocated position, gave balanced diploid nuclei and the loss was assumed to be by deletion. This led to the proposal that high-frequency deletion was provoked by, and confined to, the excess segment. In the present work it has been shown that elimination of the translocated segment in such diploids occurs more frequently by mitotic crossing over than by deletion. Accordingly, in a more rigorous test of the possible association of excess segments and deletions, a diploid homozygous for an extra, translocated segment has been studied as mitotic crossing over in this strain could not give a balanced genome. The strain was extremely unstable and gave variants of which most had a balanced, or near-balanced, diploid genome. Some variants arose by simultaneous deletions involving both non-translocated segments; almost all variants had deletions with breakpoints different from those most frequent in the corresponding, duplication haploid. The results have shown the diversity of mechanisms available for the correction of genome imbalance and that, at least in the case of Dp(I,II), the degree and modalities of mitotic instability are functions of the balance of chromosome segments and of ploidy.