Total synthesis of (+)-tedanolide

A convergent, stereocontrolled total synthesis of (+)-tedanolide (1), an architecturally complex marine antitumor macrolide, has been achieved in 31 steps (longest linear sequence). Highlights of the synthesis comprise a highly efficient dithiane union, followed by an Evans-Tishchenko "oxidation" to enable formation of the seco-ester in the presence of an oxidatively labile dithiane, a highly refined protecting group strategy, and a chemo- and stereoselective epoxidation at C(18,19).     

Physics of thick polymers

We present the results of analytical calculations and numerical simulations of the behavior of a new class of chain molecules that we call thick polymers. The concept of the thickness of such a polymer, viewed as a tube, is encapsulated by a special three‐body interaction and impacts on the behavior both locally and nonlocally. When thick polymers undergo compaction because of an attractive self‐interaction, we find a new type of phase transition between a compact phase and a swollen phase at zero temperature with increasing thickness. In the vicinity of this transition, short tubes form space‐filling helices and sheets as observed in protein native‐state structures. With increasing chain length, or with an increasing number of chains, we numerically find a crossover from secondary‐structure motifs to a quite distinct class of structures akin to the semicrystalline phases of polymers or amyloid fibers in polypeptides. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 650–679, 2005     

Fluctuation-dissipation theorem and the dynamical renormalization group

The relation between a recently introduced dynamical real-space renormalization group and the fluctuation-dissipation theorem is discussed. An apparent incompatibility is pointed out and resolved.     

The lyconadins: enantioselective total syntheses of (+)-lyconadin A and (-)-lyconadin B

A full account of the enantioselective total syntheses of (+)-lyconadin A (1) and (-)-lyconadin B (2) is presented. Central to this venture was recognition and deployment of a key strategy-level intramolecular aldol/conjugate addition cascade that led, in a single operation, to two new carbon-carbon sigma-bonds, three new stereogenic centers, and two new rings, albeit with the incorrect stereogenicity at C(12) for the lyconadins. Correction of the C(12) stereogenicity was achieved via innovative use of a protonated intramolecular aminal. An aminoiodo olefin cyclization, in conjunction with alpha-pyridinone and 3,4-dihydropyridinone annulation protocols, permitted completion of the syntheses of (+)-lyconadin A (1) and (-)-lyconadin B (2), respectively.     

Copper-catalyzed synthesis of enantioenriched tetraarylethanes

Herein we report the asymmetric synthesis of 1,2-dipyridyl-1,2-diarylethanes via an unusual Cu(I)-catalyzed dimerization reaction. Subjection of a variety of enantioenriched substituted 2-pyridyl alcohols to a one-pot protocol generates the desired products in good yields and diastereoselectivities and with ee's up to >99%.     

A second-generation total synthesis of (+)-phorboxazole A.

A highly convergent second-generation synthesis of (+)-phorboxazole A has been achieved. Highlights of the synthetic approach include improved Petasis-Ferrier union/rearrangement conditions on a scale to assemble multigram quantities of the C(11-15) and C(22-26) cis-tetrahydropyrans inscribed with the phorboxazole architecture, a convenient method to prepare E- and Z-vinyl bromides from TMS-protected alkynes utilizing radical isomerization of Z-vinylsilanes, and a convergent late-stage Stille union to couple a fully elaborated C(1-28) macrocyclic iodide with a C(29-46) oxazole stannane side chain to establish the complete phorboxazole skeleton. The synthesis, achieved with a longest linear sequence of 24 steps, proceeded in 4.6% overall yield.     

Synthesis and biological evaluation of phorboxazole congeners leading to the discovery and preparative-scale synthesis of (+)-chlorophorboxazole a possessing picomolar human solid tumor cell growth inhibitory activity

Highly convergent syntheses of eight phorboxazole congeners and their evaluation against a diverse panel of human solid tumor cancer cell lines have been achieved. Specifically, the C(45-46) alkyne, alkene, and alkane phorboxazole A analogues [(+)-4-(+)-6] were constructed and found to display single digit nanomolar cell growth inhibitory activities in a series of human cancer cell lines. The structurally simplified C(11-15)-acetal congener (+)-20Z also proved potent albeit reduced (cf. 34.6 nM) when evaluated against the same cell line panel. Importantly, (+)-C(46)-chlorophorboxazole A (3) displayed picomolar (pM) inhibitory activity in several cell lines.     

Polarization Optimality of Equally Spaced Points on the Circle for Discrete Potentials

We prove a conjecture of Ambrus, Ball and Erdélyi that equally spaced points maximize the minimum of discrete potentials on the unit circle whenever the potential is of the form $$\begin{aligned} \sum _{k=1}^n f(d(z,z_k)), \end{aligned}$$ ∑ k = 1 n f ( d ( z , z k ) ) , where $f:[0,\pi ]\rightarrow [0,\infty ]$ f : [ 0 , π ] → [ 0 , ∞ ] is non-increasing and convex and $d(z,w)$ d ( z , w ) denotes the geodesic distance between z and w on the circle.