Synthesis and biological evaluation of (-)-dictyostatin and stereoisomers

Total syntheses of (−)-dictyostatin, 6,16-bis-epi-dictyostatin, 6,14,19-tris-epi-dictyostatin, and a number of other isomers and analogs are reported. Three main fragments—top, middle, and bottom—were first assembled and then joined by olefination or anionic addition reactions. After appending the two dienes at either end of the molecule, macrolactonization and deprotection completed the syntheses. The work proves both the relative and absolute configurations of (−)-dictyostatin. The compounds were evaluated by cell-based measurements of increased microtubule mass and antiproliferative activity, and in vitro tubulin polymerization assays as well as competitive assays with paclitaxel for its binding site on microtubules. These assays showed dictyostatin to be the most potent of the agents and further showed that the structural alterations caused from 20- to >1000-fold decreases in activity.     

Solid-state 13C NMR characterization of molecular orientation of hot drawn nylon 6

Two-dimensional cross polarization (CP), magic angle spinning (MAS) rotor synchronization NMR spectroscopy has been used to determine quantitatively the molecular orientational distribution function on hot-drawn Nylon 6. Both films and fibers are studied that had been thermally deformed at temperature above T_g, from 60 to 175°C at draw ratios in the range of 1-5.5. In the two-dimensional NMR spectrum, the sidebands that intrinsically originate from the chemical shift anisotropy reveal the degree of molecular orientational order. No preferential orientational order is detected for the sample without thermal deformation, and the highest degree of order is observed for samples which have been hot drawn above T_g at ratios ca. 5. Based on the aggregate model the maximum achievable order parameters are determined. © 1994 John Wiley & Sons, Inc.     

New synthesis of 1,2,3-thiadiazole-5-thiol derivatives

New syntheses of 1,2,3-thiadiazole-5-thiol derivatives utilizing the thionyl chloride ring-closure of the aldehyde derivatives 5a, b , and c are reported.     

A novel conversion of chromone-3-carboxaldehyde to 5-nitro-2,3-benzofurandione-(Z)-2-oxime

The conversion of chromone-3-carboxaldehyde to 5-nitro-2,3-benzofurandione-($\text{Z}$)-2-oxime under nitrating conditions is reported.     

Efficient synthesis of novel gamma-substituted gamma-butenolides by Lewis acid catalyzed addition of metal enolates of active methylene compounds to mucohalic acids

Lewis acid catalyzed addition of active methylene compounds to mucochloric acid (1) and mucobromic acid (2) affording Knoevenagel aldol adducts, gamma-substituted gamma-butenolides, has been explored. Catalytic efficiencies of various Lewis acids have been compared. Indium acetate (0.25-5 mol %) was found to be the most efficient catalyst.     

An efficient step size control for continuation methods

In solving a nonlinear equation by the use of a continuation method one of the crucial problems is the choice of the step sizes. We present a model for the total computational cost of a standard numerical continuation process and solve the problem of optimal step size control for this model. Using the theoretical results as a basis, we develop an adaptive step size algorithm for Newton's method. This procedure is computationally inexpensive and it gives quite satisfactory results compared to some other numerical experiments found in the literature.     

The dichlorovinylation of enolates

The condensation of certain ketone and ester enolates with trichloroethylene proceeds with surprising ease to yield dichlorovinylation products. The $\text{trans}$ stereochemistry for one such product is established by X-ray, and subsequent transformations of these initial products to ethinyl or ω-chloroethinyl derivatives is described.