1,3-Dimethyl-3′,5-diphenyl-1,5-dihydro-2H,5′H-spiro[furo[2,3-d]pyrimidine-6,4′-isoxazole]-2,4,5′(3H)-trione

Michael addition–halogenation–intramolecular ring-closing (MHIRC) reactions are processes in which a halogen atom as a leaving group can attach to substrates or reactants during the reaction, which then undergoes intramolecular ring closure. In this communication the MHIRC transformation of 4-benzylidene-3-phenylisoxazol-5(4H)-one and 1,3-dimethylbarbituric acid in the presence of N-bromosuccinimide and sodium acetate in EtOH at room temperature was carefully investigated to give novel 1,3-dimethyl-3′,5-diphenyl-1,5-dihydro-2H,5′H-spiro[furo[2,3-d]pyrimi- dine-6,4′-isoxazole]-2,4,5′(3H)-trione in a good yield. The structure of the new compound was confirmed by the results of elemental analysis as well as mass, nuclear magnetic resonance, and infrared spectroscopy.

Diverse mechanisms regulate contractile ring assembly for cytokinesis in the two-cell C. elegans embryo

Cytokinesis occurs at the end of mitosis due to the ingression of a contractile ring that cleaves the daughter cells. The core machinery regulating this crucial process is conserved among metazoans. Multiple pathways control ring assembly, but their contribution in different cell types is not known. We found that in the C. elegans embryo, AB and P1 cells fated to be somatic tissue and germline, respectively, have different cytokinesis kinetics supported by distinct myosin levels and organization. Through perturbation of RhoA or polarity regulators and the generation of tetraploid strains, we found that ring assembly is controlled by multiple fate-dependent factors that include myosin-levels, and mechanisms that respond to cell size. Active Ran coordinates ring position with the segregating chromatids in HeLa cells by forming an inverse gradient with importins that control the cortical recruitment of anillin. We found that the Ran pathway regulates anillin in AB cells, but functions differently in P1 cells. We propose that ring assembly delays in P1 cells caused by low myosin and Ran signaling coordinate the timing of ring closure with their somatic neighbours.

Alkynedicobalt Mediated Vinylogous Nazarov Reactions

The SnCl4 mediated reactions of cross conjugated aryl enynone-Co2(CO)6 and dienynone-Co2(CO)6 complexes afford benzocycloheptynone complexes or cycloheptenynone complexes in a thermal vinylogous Nazarov process. The rate of ring closure is...

Peptide cyclisation promoted by supramolecular complex formation

Phenol ester activated dipeptides that are reluctant to ring-closure have been cyclised with the aid of sterically shielding metallo-porphyrins avoiding unwanted intermolecular reactions. The binding of ZnTPP to the dipyridine-functionalised...

Cyclic Poly(ß-amino ester)s with Enhanced Gene Transfection Activity Synthesized through Intra-molecular Cyclization

Topological structure plays a critical role in gene delivery of cationic polymers. Cyclic poly(ß-amino ester)s (CPAEs) are successfully synthesized via sequential Michael addition and free radical initiating ring-closure reaction. CPAE...

Mechanistic analysis of carbon–carbon bond formation by deoxypodophyllotoxin synthase

Deoxypodophyllotoxin contains a core of four fused rings (A to D) with three consecutive chiral centers, the last being created by the attachment of a peripheral trimethoxyphenyl ring (E) to ring C. Previous studies have suggested that the iron(II)- and 2-oxoglutarate–dependent (Fe/2OG) oxygenase, deoxypodophyllotoxin synthase (DPS), catalyzes the oxidative coupling of ring B and ring E to form ring C and complete the tetracyclic core. Despite recent efforts to deploy DPS in the preparation of deoxypodophyllotoxin analogs, the mechanism underlying the regio- and stereoselectivity of this cyclization event has not been elucidated. Herein, we report 1) two structures of DPS in complex with 2OG and (±)-yatein, 2) in vitro analysis of enzymatic reactivity with substrate analogs, and 3) model reactions addressing DPS’s catalytic mechanism. The results disfavor a prior proposal of on-pathway benzylic hydroxylation. Rather, the DPS-catalyzed cyclization likely proceeds by hydrogen atom abstraction from C7', oxidation of the benzylic radical to a carbocation, Friedel–Crafts-like ring closure, and rearomatization of ring B by C6 deprotonation. This mechanism adds to the known pathways for transformation of the carbon-centered radical in Fe/2OG enzymes and suggests what types of substrate modification are likely tolerable in DPS-catalyzed production of deoxypodophyllotoxin analogs.

Cyclization Reactions Involving 2-Aminoarenetellurols and Derivatives of α,β-Unsaturated Carboxylic Acids

The reductive cyclization of arenetellurols carrying α,β-unsaturated amide functionalities in the ortho position was investigated. Conceptually, such compounds can form 1,3-tellurazoles without the involvement of the unsaturation in the ring closure, they can form 1,4-tellurazinone derivatives, or they can undergo ring closure to 1,5-tellurazepinones. Amides derived from acrylic and methacrylic acid generated 1,5-tellurazepinones while 2-cinnamylamidobenzenetellurol cyclized to a 1,3-tellurazole derivative. In contrast, the reaction of acetylenedicarboxylic acid and its derivatives with 2-aminoarenetellurols generated 1,4-tellurazepinones, including a derivative of novel tricyclic naphtho [1, 4]tellurazinone. A comparison with analogous reactions of sulfur congeners indicates that their chemistry is a good predictor for the products obtained from 2-aminoarenetellurols. Selected compounds were characterized by X-ray crystallography. The present work offers access to previously unexplored organotellurium heterocycles.