Practical Synthesis of α,α-Dibromo Esters from Aldehydes.

Herein, we report an efficient and practical method for synthesizing α,α-dibromo esters, which are the precursors of ynolates, through the dibromination of aldehydes followed by oxidative esterification using iodine. Our method was successfully employed in a large-scale synthesis to yield more than 30 g of dibromo esters. These two steps can be performed in a one-pot manner, which makes the method adaptable even for aldehydes having low boiling points.

A Strategy Based on "Ambident Anthracene" for the Synthesis of Higher-Order Iptycenes.

Invited for the cover of this issue is the group of Takayuki Iwata and Mitsuru Shindo at Kyushu University. The image depicts the longest-chain iptycene synthesized in this study, showing the connections between iptycene synthetic units by using transparent cases. Read the full text of the article at 10.

A Strategy Based on "Ambident Anthracene" for the Synthesis of Higher-Order Iptycenes.

An efficient method for the synthesis of higher-order iptycenes using an "ambident anthracene" building block is presented. For that purpose, an iterative elongation strategy involving the ring-opening of an endoxide to give a highly reactive anthranoxide, followed by a Diels-Alder reaction with an aryne was used. The method systematically provides higher-order iptycenes, including trideciptycene, which is currently the iptycene with the longest chain to have been synthesized.

Design and synthesis of strong root gravitropism inhibitors with no concomitant growth inhibition.

Herein, we describe a highly potent gravitropic bending inhibitor with no concomitant growth inhibition. Previously, we reported that (2Z,4E)-5-phenylpenta-2,4-dienoic acid (ku-76) selectively inhibits root gravitropic bending of lettuce radicles at 5 μM. Based on the structure-activity relationship study of ku-76 as a lead compound, we designed and synthesized various C4-substituted analogs of ku-76.

Retro-Friedel-Crafts-Type Acidic Ring-Opening of Triptycenes: A New Synthetic Approach to Acenes.

Invited for the cover of this issue is the group of Takayuki Iwata, Mitsuru Shindo, and co-workers at Kyushu University. The image depicts ring-opening of triptycenes to afford corresponding anthrones by acid treatment. Read the full text of the article at 10.

Retro-Friedel-Crafts-Type Acidic Ring-Opening of Triptycenes: A New Synthetic Approach to Acenes.

The triptycene scaffold has been ring-opened by using a retro-Friedel-Crafts-type reaction under acidic conditions to give its corresponding anthrone product. 9-Hydroxytriptycenes and unsubstituted triptycene undergo ring-opening reaction under strongly acidic conditions, such as with TfOH. An investigation of the substitution effect has revealed that the electron-donating group on the arene moiety allows the reaction to proceed in the presence of a weaker acid, such as TFA.

Taxonomic Reassessment of the Izumo Lineage of : Description of a New Species from Chugoku, Japan.

Here, we describe a new species of the genus from Chugoku, Japan. In populations from central to eastern Shimane Prefecture, the Izumo Lineage of was clearly distinguished from the true based on morphological and molecular evidence. Thus, we describe the former lineage as a new species, sp.

Quadruple Role of Pd Catalyst in Domino Reaction Involving Aryl to Alkyl 1,5-Pd Migration to Access 1,9-Bridged Triptycenes.

A Pd-catalyzed domino reaction of 1,8,13-tribromo-9-methoxytriptycenes is reported. Under conventional Suzuki coupling conditions, the triptycenes underwent multiple transformations to give 1,9-bridged triptycenes. Based on mechanistic investigations, a single Pd catalyst functions as Pd , Pd and Pd species to catalyze four distinct processes: (1) aryl to alkyl 1,5-Pd migration, (2) intramolecular arylation, (3) homocoupling of phenylboronic acid and (4) Suzuki coupling.

Design and chemical synthesis of root gravitropism inhibitors: Bridged analogues of ku-76 have more potent activity.

Previously, we found (2Z,4E)-5-phenylpenta-2,4-dienoic acid (ku-76) to be a selective inhibitor of root gravitropic bending of lettuce radicles at 5 μM, with no concomitant growth inhibition, and revealed the structure-activity relationship in this inhibitory activity. The conformation of ku-76 is flexible owing to the open-chain structure of pentan-2,4-dienoic acid with freely rotating single bonds, and the (2Z)-alkene moiety may be isomerized by external factors. To develop more potent inhibitors and obtain insight into the target biomolecules, various analogues of ku-76, fixed through conformation and/or configuration, were synthesized and evaluated.

Anthranoxides as Highly Reactive Arynophiles for the Synthesis of Triptycenes.

We report herein an efficient method to synthesize triptycenes by the reaction of benzynes and anthranoxides, which are electron-rich and readily prepared from the corresponding anthrones. Using this method, 1,9-syn-substituted triptycenes were regioselectively obtained employing 3-methoxybenzynes. This method was also applied to synthesize pentiptycenes.

Essential structural features of (2Z,4E)-5-phenylpenta-2,4-dienoic acid for inhibition of root gravitropism.

Previously, we found (2Z,4E)-5-phenylpenta-2,4-dienoic acid (ku-76) to be a selective inhibitor of root gravitropic bending of lettuce radicles at 5 μM, with no concomitant growth inhibition. Here, we describe a structure-activity relationship study of ku-76 to determine the essential structural features for the inhibitory activity. A series of ku-76 analogues was synthesized and the key features of ku-76 that are necessary for inhibition of lettuce root gravitropic bending were determined.

Synthesis of Distorted 1,8,13-Trisilyl-9-hydroxytriptycenes by Triple Cycloaddition of Ynolates to 3-Silylbenzynes.

1,8,13-Trialkyl(aryl)silyl-9-hydroxytriptycenes (trisilyltriptycenes) were synthesized by the triple addition of ynolates and 3-silylbenzynes with high regioselectivity. Benzene rings in the resulting triptycenes were highly distorted where the dihedral angles between the substituents were as high as 35°. The distortion energy induced step-by-step halogenation reactions to yield halogenated triptycenes, including chiral triptycenes.

Synthesis of Ynolates via Double Deprotonation of Nonbrominated Esters.

Herein, we report a double deprotonation method used for the preparation of ynolates starting from nonbrominated 2,6-di--butylphenyl esters. The current method is superior to the previously described double lithium/halogen exchange approach because easily accessible starting materials are used. This method will be especially useful for preparation of ynolates bearing functional groups in organic synthesis.

Asymmetric Synthesis of Gonytolide A: Strategic Use of an Aryl Halide Blocking Group for Oxidative Coupling.

The first synthesis of the chromanone lactone dimer gonytolide A has been achieved employing vanadium(V)-mediated oxidative coupling of the monomer gonytolide C. An o-bromine blocking group strategy was employed to favor para- para coupling and to enable kinetic resolution of (±)-gonytolide C. Asymmetric conjugate reduction enabled practical kinetic resolution of a chiral, racemic precursor and the asymmetric synthesis of (+)-gonytolide A and its atropisomer.

Asymmetric Total Synthesis of (-)-Stemonamine and Its Stereochemical Stability.

The first asymmetric total synthesis of (-)-stemonamine is described. The key reactions included intramolecular acylation to construct the seven-membered ring and a tandem [2+2] cycloaddition-Dieckmann condensation reaction using an ynolate to form the fully substituted cyclopentenone moiety. Racemization and epimerization of the natural product were first experimentally demonstrated.

Regioselective One-Pot Synthesis of Triptycenes via Triple-Cycloadditions of Arynes to Ynolates.

We developed the novel one-pot synthetic method of substituted triptycenes by the reaction of ynolates and arynes. This four-step process involves three cycloadditions and electrocyclic ring opening of the strained Dewar anthracene. Each of the three related but structurally distinct classes of nucleophiles (ynolate, enolate, and anthracenolate) reacts with o-benzyne in the same predictable manner controlled by chelation and negative hyperconjugation.

One-Pot Evolution of Ageladine A through a Bio-Inspired Cascade towards Selective Modulators of Neuronal Differentiation.

A bio-inspired cascade reaction has been developed for the construction of the marine natural product ageladine A and a de novo array of its N1-substituted derivatives. This cascade features a 2-aminoimidazole formation that is modeled after an arginine post-translational modification and an aza-electrocyclization. It can be effectively carried out in a one-pot procedure from simple anilines or guanidines, leading to structural analogues of ageladine A that had been otherwise synthetically inaccessible.

Syntheses of Dimeric Tetrahydroxanthones with Varied Linkages: Investigation of "Shapeshifting" Properties.

The 2,4'- and 4,4'-linked variants of the cytotoxic agent secalonic acid A and their analogues have been synthesized. Kinetic resolution of an unprotected tetrahydroxanthone scaffold followed by copper-mediated biaryl coupling allowed for efficient access to these compounds. Evaluation of the "shapeshifting" properties of 2,2'-, 2,4'-, and 4,4'-linked variants of the secalonic acids A in a polar solvent in conjunction with assays of the compounds against select cancer cell lines was conducted to study possible correlations between linkage variation and cytotoxicity.

Design, synthesis and evaluation of a boronic acid based artificial receptor for (L)-DOPA in aqueous media.

Design and synthesis of a boronic acid based artificial receptor which selectively and effectively bound to a neurotransmitter, l-DOPA (), in aqueous media. In addition, the synthetic receptor was found to effectively inhibit the DDC (l-DOPA decarboxylase) enzymatic reaction under physiological conditions.

A conformationally fixed analog of the peptide mimic Grb2-SH2 domain: synthesis and evaluation against the A431 cancer cell.

A small peptide mimic of the Grb2-SH2 domain, which was previously prepared through the template-assisted click approach and exhibited selective A431 tumor growth inhibition both in vitro and in vivo, was further elaborated on to enhance the interaction with target phosphorylated proteins. A conformationally fixed analog was efficiently synthesized by solid-supported ring-closing metathesis and Cu(i)/His-mediated self-activating Huisgen [3+2] cycloadditon as the key steps, and exhibited a 10-fold enhanced affinity to a phosphorylated peptide, a truncated peptide analog of the Grb2-SH2-interacting phosphoproteins. A stronger interaction with the target phosphorylated proteins gave this cyclic analog cytotoxic activity in A431 cells.

Cell surface biotinylation by azaelectrocyclization: easy-handling and versatile approach for living cell labeling.

Versatile method for living cell labeling has been established. Cell surfaces are initially biotinylated by azaelectrocyclization, and then treated with the fluorescence-labeled avidin or the anti-biotin antibody.