Cyclative Cleavage Research Articles

Ring closing metathesis in organic synthesis: Evolution of a high speed, solid phase method for the preparation of β-turn mimetics

Complimentary solid phase syntheses of the Freidinger lactam class of β-turn mimetics have been developed using ring closing metathesis as both the key carbon-carbon bond forming step and the cyclative cleavage mechanism. Solid phase variants of the Fukuyama-Mitsunobu process were utilized as part of a rapid three-step sequence to construct immobilized lactam precursors. An alternative solid phase process is offered which utilizes an Ugi/ring closing metathesis reaction tandem to deliver the desired compounds in two synthetic operations.

Solid-phase synthesis of cyclic imides.

A cyclative cleavage strategy for the synthesis of cyclic imides on a polystyrene resin is described. After optimization of the cleavage conditions, a small array of succinimides and phthalimides was synthesized. The methodology was then applied to a drug discovery project, in which it was used to synthesize a new class of delta-opioid receptor ligand by both automated and manual methods.

Solid-phase synthesis of pyrrolidines employing a cyclisation–cleavage strategy

The solid-phase synthesis of several pyrrolidines has been realised utilising imino-Sakurai and palladium-catalysed cyclisation–cleavage reactions as key steps.

Solid Phase Synthesis of 3-Acyl-2,4-Pyrrolidinediones (3-Acyl Tetramic Acids) via Mild Cyclative Cleavage

The solid phase synthesis of 3-acyl-2,4-pyrrolidinediones (3-acyl tetramic acids) has been reported. Cyclative cleavage of the penultimate intermediative via a Dieckmann cyclization yields the 3-acyl-2,4-pyrrolidinediones. Remarkably mild conditions are required for the cyclative cleavage; treatment of the resin-bound acyclic precursor with one equivalent of potassium hydroxide in methanol at room temperature for 5-30 minutes affords the product. The synthetic route routinely provides high yields in greater than 95% purity and is compatible with acid-labile protecting groups. Virtually any hydroxy-functionalized resin can be utilized for this synthesis.

Solid-phase combinatorial synthesis of 4-hydroxyquinolin-2(1 H)-ones

Cyanoacetic acid was loaded on Wang resin and C-acylated using acid anhydrides and triethylamine as base. Resin cleavage with concomitant decarboxylation produces β-keto nitriles. In the case of isatoic anhydrides, the resin-bound acylated intermediates undergo cyclative cleavage upon heating, leading to 4-hydroxyquinolin-2(1 H)-ones.

Solid phase synthesis of 1-aminohydantoin libraries

The solid support synthesis of a series of 1-aminohydantoins based on a diverse set of hydrazino amino acids, aldehydes, and amines is described. The method involves the construction of resin attached hydrazino acid precursors, followed by subsequent derivatization, and then cyclizative cleavage off the resin. Overall yields vary per example between 15 and 60% and the samples are suitable for biological evaluations without further purification.

A second generation solid phase approach to Freidinger lactams: Application of Fukuyama's amine synthesis and cyclative release via ring closing metathesis

Abstract A high-speed solid phase synthesis of Freidinger lactams was accomplished using a novel variant of Fukuyama's amine synthesis and ring closing metathesis-promoted cyclative cleavage as key steps.

Solid phase heterocyclic synthesis via ring closing metathesis: Traceless linking and cyclative cleavage through a carbon-carbon double bond

Ring closing metathesis was utilized to affect cyclative cleavage of resin-bound α,ω dienes in the solid phase synthesis of dihydropyarans, pipecolinic acid derivatives and Freidinger lactams.

Cyclo(-arginyl-sarcosyl-aspartyl-phenylglycyl-)2. Simple synthesis of an RGD-related peptide with inhibitory activity for platelet aggregation

The dimerization–cleavage of the tetrapeptide precursor bound to the benzophenone oxime resin afforded cyclo[-Arg(Tos)-Sar-Asp(OcHex)-Phg-]2, a cyclic analogue of the RGD peptide. The yield and the selectivity between the tetra-/octa-peptide formed through the cyclization–cleavage depended on the sequence of the tetrapeptide. The ratio of tetra-/octa-peptide also depended on the substitution level of the oxime resin with the peptide segment. The cyclic octapeptide was also synthesized through the solution-phase dimerization–cyclization from the linear tetrapeptide precursor. The solution-phase dimerization–cyclization was very efficiently mediated with BOP/HOBt as the condensation reagent. 1H NMR and CD spectra suggested that the cyclic octapeptide was of some restricted conformation, which might be involved in the preferred formation of the octapeptide in both solid- and solution-phase syntheses. The octapeptide showed potent inhibitory activity toward platelet aggregation; however, it showed no activity toward cell adhesion.

ChemInform Abstract: Efficient Preparation of Cyclic Peptide Mixtures by Solid Phase Synthesis and Cyclization Cleavage with Oxime Resin.

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Efficient Preparation of Cyclic Peptide Mixtures by Solid Phase Synthesis and Cyclization Cleavage with Oxime Resin

A mixture of cyclic peptides, cyclo(-Arg-Gly-Asp-Xaa-Aca-) (Xaa, 10 amino aids; Aca, ε-aminocaproic acid), and another mixture of related peptides were efficiently synthesized by the solid-phase synthesis and cyclization-cleavage method with oxime resin.

Efficient preparation of cyclic peptide mixtures by solid phase synthesis and cyclization cleavage with oxime resin

A mixture of cyclic peptides, cyclo(-Arg-Gly-Asp-Xaa-Aca-) (Xaa, 10 amino aids; Aca, ε-aminocaproic acid), and another mixture of related peptides were efficiently synthesized by the solid-phase synthesis and cyclization-cleavage method with oxime resin.

Gc-Ms Analysis of Photodegradation Products of Dichlophop-Methyl

Abstract The photochemical transformation products of 2-[4-(2,4-dichlorphenoxyphenylen]propionic acid methyl ester (I). the active ingredient of the herbicide Dichlophop methyl (trade mark Illoxane) after irradiation with Hg (λmax=254 nm) and Xe (λ>290 nm) lamps in solution, in thin film on the glass surface and in soil were studied by GC-MS. The main photodegradation pathway was found to be reductive and oxidative dechlorination, intramolecular cyclisation and ester bonds cleavage. The photodegradation of Illoxane is considered as a model for chlorophenoxy pesticides degradation and toxic methabolites formation in the environment.

Facile synthesis of cyclic peptides containing α-aminosuberic acid with oxime resin

Cyclic peptides containing an α-aminosuberic acid unit are conveniently synthesized by solid-phase synthesis followed by cyclization cleavage with Kaiser's oxime resin.

Reaction of cardiac myosin with a purine disulfide analog of adenosine triphosphate. II. Stoichiometry and subunit location of labeling.

The reaction of bovine cardiac myosin with the site-specific purine disulfide analog of ATP, 6,6'-dithiobis (inosinyl imidodiphosphate), was studied to determine the stoichiometry of labeling and subunit location of the reactive cysteines. The analog inactivates myosin by forming a mixed disulfide between the thiopurine nucleotide and certain key cysteines. The thiopurine nucleotide was displaced quantitatively by 14CN to form the more stable thiocyanato-enzyme derivatives. In cardiac myosin, the reactive cysteines could be categorized into three classes, nonessential, critical, and noncritical. The modification of the critical cysteines (two per myosin) inactivated the EDTA and Ca2+ ATPase activities, the latter to a lesser extent. The nonessential cysteines (two to three per myosin) and the noncritical cysteines (two per myosin), differentiated by their rates of reaction, had no effect on the ATPase activities after modification. Thiocyanato-modified myosin was analyzed by sodium dodecyl sulfate gel electrophoresis to determine the distribution of 14CN in the subunits. The critical cysteines were found on the 21,000-dalton light chain (LC1) and the noncritical cysteines on the heavy chains. More specifically, the critical cysteine modified in cardiac LC1 (determined from the products after cyclization and chain cleavage at the thiocyanatoalanyl residues) was shown to be the thiol residue whose surrounding amino acid sequence is homologous to that of the single cysteine of the skeletal myosin alkali light chains, confirming the likely similar structure and function of these light chains in the two different muscle types.