Robert S. Coleman

The total synthesis of the tubulin-binding agents ceratamine A and B is reported, along with des-methyl analogs, via a synthetic route that is high-yielding and operationally efficient. The synthetic route involved a Beckmann rearrangement to form an azepine ring precursor, a Knoevenagel condensation to install the benzylic side chain, and an effective imidazole annulation onto an α-aminoketone precursor with a protected S-methylisothiourea. Final dehydrogenation proved remarkably facile using IBX.

DNA is depicted in elementary chemistry and biology texts as a perfect double helix; but local structural variations and nanoscale motions within the double helix are critical for its ability to be packaged, recognized, and transcribed. DNA is becoming a favored nanoscale assembly tool due to the precise pairing of complementary strands that in principle can bring nanoscale objects within a well-defined distance of each other. However, future nanotechnology applications of DNA need to take into account its variable nanoscale structural and dynamic properties, especially in terms of its solvent shell and counterions. This article highlights efforts of the authors to (1) interrogate nanoscale structures of DNA using nanoparticles and (2) measure the dynamic nature of DNA over six orders of magnitude in time, using a fluorescent reporter in the base stack.

The design and synthesis of a detailed series of functional “top-half” substructures of azinomycin A and B is described.

Evaluation of the importance of C18/C19 stereochemistry of azinomycin A/B epoxyamide partial structures with respect to DNA alkylation sequence selectivity is reported using a unique assay with a DNA oligomer containing imbedded normal (5‘-GGC-3‘/3‘-CCG-5‘) and inverted (5‘-CGG-3‘/3‘-GCC-5‘) azinomycin consensus cross-linking sequences. Both species were found to have unique selectivity profiles and alkylate DNA in a manner distinct from azinomycin B. Computational docking experiments support altered binding modes for the enantiomers.

Convergent and efficient syntheses of the microbial natural products gymnoconjugatin A and B are reported and were based on a linchpin coupling strategy using a boron/tin hetero-bis-metallated butadiene system.

The dynamics of the electric fields in the interior of DNA are measured by using oligonucleotides in which a native base pair is replaced by a dye molecule (coumarin 102) whose emission spectrum is sensitive to the local electric field. Time-resolved measurements of the emission spectrum have been extended to a six decade time range (40 fs to 40 ns) by combining results from time-correlated photon counting, fluorescence up-conversion, and transient absorption. Recent results showed that when the reporter is placed in the center of the oligonucleotide, the dynamics are very broadly distributed over this entire time range and do not show specific time constants associated with individual processes (Andreatta, D.; et al. J. Am. Chem. Soc.2005, 127, 7270). This paper examines an oligonucleotide with the reporter near its end. The broadly distributed relaxation seen before remains with little attenuation. In addition, a new relaxation with a well-defined relaxation time of 5 ps appears. This process is assigned to the rapid component of “fraying” at the end of the helix.

An efficient, six-step stereocontrolled total synthesis of the antifungal agent strobilurin B is reported and was based on a convergent bi-directional coupling featuring a hetero-bis-1,4-metallated pentadiene system as the linchpin.

Hetero-bis-metalated 1,3-butadiene is employed in the lynchpin coupling of synthetic fragments of the side chain of the antitumor agent, lucilactaene. Sequential Stille and Suzuki−Miyaura couplings interpolate this unique boron/tin diene into the pentaene chain. The total synthesis of lucilactaene was accomplished efficiently, in just eight linear steps.

Full details of the asymmetric total syntheses of the dibenzocyclooctadiene lignans interiotherin A, angeloylgomisin R, gomisin O, and gomisin E (epigomisin O) are presented. The syntheses were based on a unified synthetic strategy involving a novel crotylation using the Leighton auxiliary that occurred with excellent asymmetric induction (>98:2 enantiomeric ratio), a diastereoselective hydroboration/Suzuki−Miyaura coupling reaction sequence, and an atropdiastereoselective biarylcuprate coupling, both of which occurred with total (>20:1) stereocontrol. The syntheses were achieved in six to eight steps from simple aromatic precursors.