Nickel‐Catalyzed Barton Decarboxylation and Giese Reactions: A Practical Take on Classic Transforms

Two named reactions of fundamental importance and paramount utility in organic synthesis have been reinvestigated, the Barton decarboxylation and Giese radical conjugate addition. N ‐hydroxyphthalimide (NHPI) based redox‐active esters were found to be convenient starting materials for simple, thermal, Ni‐catalyzed radical formation and subsequent trapping with either a hydrogen atom source (PhSiH₃) or an electron‐deficient olefin. These reactions feature operational simplicity, inexpensive reagents, and enhanced scope as evidenced by examples in the realm of peptide chemistry.     

Synthesis of polymers having a phospholipid polar group connected to a poly(oxyethylene) chain and their protein adsorption-resistance properties

New methacrylates having a phospholipid polar group which was connected to various lengths of poly(oxyethylene) chains to form a polymerizable group (MEOnPC) were synthesized. The MEOnPC could polymerize with n-butyl methacrylate (BMA) in ethanol using a conventional radical polymerization technique. The unit mole fraction of MEOnPC in the polymer corresponded to that in the feed monomer solution. The MEOnPC polymers were soluble in ethanol, insoluble in water, but swelled in water and became hydrated. On the surface of a poly(BMA) membrane coated with MEOnPC, the phosphorylcholine groups of the MEOnPC unit present were determined by x-ray photoelectron spectroscopy. As a fundamental evaluation for biomedical materials, adsorption of one of the plasma proteins, fibrinogen, on acrylic beads coated with the MEOnPC polymers was evaluated. The amount of fibrinogen adsorbed on the MEOnPC polymer was smaller than that on the original acrylic beads, poly(BMA) and poly(2-hydroxyethyl methacrylate). The increase in the MEOnPC unit mole fraction in the polymer showed more effective protein adsorption-resistant properties. © 1996 John Wiley & Sons, Inc.     

A novel polyaddition of bifunctional acetylenes containing electron-withdrawing groups. III. Synthesis of polymers having β-alkoxyenoate moieties by the reaction of internal diynes with diols

Tri-n-butylphosphine-catalyzed polyadditions of activated internal diynes (bifunctional β-substituted propiolate, 1B and 1C ) with diols are described. Although a terminal bispropiolate ( 1A ) could not produce soluble polymers, with secondary diols, the polyaddition of 1B or 1C with primary as well as secondary diols gave corresponding polymers ( 3 , only composed of E isomeric units) in high yield. The rate of the present polyaddition was estimated by a model reaction of benzyl alcohol with methyl 2-heptynoate ( 4 ), from which the introduction of alkyl groups at the β-position of propiolate moieties was found to decrease the rate of the reaction by 80 times. Furthermore, the rate-determining step on this polymerization system was speculated to be a protonation step of zwitterionic intermediates with protons from diols. © 1996 John Wiley & Sons, Inc.     

Effect of cholesterol or phospholipid incorporation on the chemical stability of the muramyldpeptide derivative B30-MDP in mixed vesicles

Application of the muramyldipeptide derivative B30-MDP to liposomal vaccines will aid in the development of improved high immunogenicity vaccines. To give full play to the effectiveness of B30-MDP as a liposomal vaccine, it is important to evaluate the effect of cholesterol, dimyristoylphosphatidylcholine (DMPC) or distearoylphosphatidylcholine (DSPC) incorporation on the chemical stability of B30-MDP and physicochemical properties of B30-MDP/lipid mixed vesicles from the view point of pharmaceutics.The observed degradation rate constants of B30-MDP by hydrolysis in B30-MDP/cholesterol mixed vesicles were increased with increasing concentration of cholesterol, however, those in B30-MDP/DMPC and B30-MDP/DSPC mixed vesicles were unchanged with increasing concentration of DMPC and DSPC. The degradation behavior of B30-MDP was then compared with physicochemical properties of B30-MDP/lipid mixed vesicles, such as membrane fluidity and particle size. It was apparent that the degradation of B30-MDP in B30-MDP/cholesterol mixed vesicles was influenced by the particle size, but not by the fluidity of the membranes. In the case of B30-MDP/phospholipid mixed vesicles, MDP/phospholipid mixed vesicles, the degradation of B30-MDP was not influenced by either the membranes' fluidity or the particle size of the mixed vesicles.It is considered that the degradation of B30-MDP in the mixed vesicles is dependent on the membrane state, and the addition of cholesterol to B30-MDP vesicle inhibits the mutual interaction of MDP regions, whereas the addition of phospholipids hardly influences the mutual interaction of MDP regions, possibly owing to phase separation between B30-MDP and phospholipids.     

Synthesis and characterization of novel polymer-drug conjugate based on the anhydride containing copolymer as a potential method for drug carrier

5-Fluorouracil (5FU) is in clinical use as an antitumor agent for the treatment of several types of solid tumors and cancers. However, development of drug resistance within the tumor cells and side effects has been a major limitation for the clinical use of 5FU. Preparation polymer-5FU conjugation is a promising potential antitumor drug and alternative pathway that could be used to treatment of cancer. For this purpose, water soluble poly(maleic anhydride-alt-N-vinyl pyrrolidone)[Poly(MA-alt-NVP)] is synthesized via charge transfer complex (CTC) copolymerization with benzoyl peroxide as an initiator at 80°C under nitrogen atmosphere. CTC mechanism is formed between through MA and NVP by determined using Uv-vis spectroscopy. Molar absorption coefficient (?^AD) and equilibrium constant (K^AD) of the complex are determined by Scott equation. The results obtained from indicate that copolymerization of MA:NVP system is preceded via alternating mechanism. The compositions of synthesized copolymers are also investigated by elemental analysis and the reactivity ratios of these monomers are calculated by using the elemental analysis data through Kelen-Tüdös, Mayo-Lewis, Fineman-Ross and Inverted Fineman-Ross equations. For preparation of polymer-drug conjugate, chemical modification is employed between the copolymer and 5FU. Polymer-drug conjugate and conjugation mechanism are enlightened by ATR-FTIR, NMR, HR-Raman and XRD methods.     

Isatindolignanoside A,a glucosidic indole-lignan conjugate from an aqueous extract of the Isatis indigotica roots

A glucosidic indole-lignan conjugate with a novel carbon skeleton, named isatindolignanoside A (1), was isolated from an aqueous extract of the Isatis indigotica roots “ban lan gen”. Its structure was determined by comprehensive analysis of spectroscopic data, enzyme hydrolysis, and electronic CD calculations. Compound 1 is active against Coxsackie virus B3 and represents the first example of natural product having a structural feature of conjugation between indole and lignan, and its plausible biosynthetic pathway is postulated.     

An Efficient Method for the Conjugation of Hydrophilic and Hydrophobic Components by Solid‐Phase‐Assisted Disulfide Ligation

Chemical conjugation between hydrophilic and hydrophobic components is difficult because of their extremely different solubility. Herein, we report a new versatile method with a solid‐phase‐assisted disulfide ligation to overcome the difficulty of conjugation attributed to solubility. The method involves two steps in a one‐pot process: 1) loading of a hydrophobic molecule onto a resin in an organic solvent, and 2) release of the solid‐supported hydrophobic molecule as a conjugate with a hydrophilic molecule into an aqueous solvent. This strategy allows the use of a suitable solvent system for the substrates in each step. Conjugates of a water‐insoluble drug, plinabulin, with hydrophilic carriers that could not be prepared by solution‐phase reactions were obtained in moderate yields (29–45 %). This strategy is widely applicable to the conjugation of compounds with solubility problems.     

Asymmetric Photochemical Synthesis of Chiral 5‐(R)‐(l)‐Menthyloxy‐4‐Cycloaminobutyrolactones

Through photocatalysed regiospecific and stereoselective additions of cycloamines to 5‐(R)‐(l)‐menthyloxy‐2 (5H)‐furanone (3), chiral 5‐(R)‐(l)‐menthyloxy‐4‐cycloaminobutyrolactones were synthesized. In the new asymmetric photoaddition of compound 3, the N‐methyl cyclic amines (4) gave novel chiral C? C photoadducts (5) in 24–50% isolated yields with d. e. ≥ 98%. However, the secondary cyclic amines (6) afforded optically active N? C photoadducts (7) in 34–58% isolated yields with d. e. ≥ 98% under the same condition. All the synthesized optically active compounds were identified on the basis of their analytical data and spectroscopic data, such as [α]₅₈₉²⁰, IR, ¹H NMR, ¹³C NMR, MS and elementary analysis. The photosynthesis of chiral butyrolactones and its mechanism were discussed in detail.     

CsF–Si(OEt)4 catalyzed addition of (hetero)aromatic amides to ethyl acrylate

The conjugate addition of some (hetero)aromatic amides to an α,β‐unsaturated ester (ethyl acrylate) proceeds efficiently in the presence of an equimolar amount of the CsF–Si(OEt)₄ system to afford the corresponding ethyl esters of N‐substituted β‐amino acids. Copyright © 2001 John Wiley & Sons, Ltd.