Protecting Group-Free Total Synthesis of (-)-Boscartin H.

Herein, we report the first protecting group-free total synthesis of (-)-boscartin H, which features a 5-12-5-fused tricyclic structure. The key steps, which include a diastereoselective THF-ring-forming/aldol reaction sequence and ring-closing metathesis, afforded high stereoselectivity with (-)-boscartin H obtained in 3.6% overall yield using a 11-step long linear sequence.

Total synthesis of 14-membered ring β-resorcylic acid lactone (+)-monocillin II.

This study outlines the total synthesis of (+)-monocillin II, wherein a -isomer selectively produces a -isomer during the ring-closing metathesis. The Mitsunobu reaction conducted at -60 °C, facilitating the formation of an ester bond, was the key to completing the total synthesis, which was accomplished in the longest linear sequence of 10 steps with an overall yield of 9.3%.

Enantioselective Total Syntheses of (+)-Ganocin A and (-)-Cochlearol B.

Herein, we report the total syntheses of (+)-ganocin A and (-)-cochlearol B, featuring pentacyclic skeletons, in optically active forms. We utilized asymmetric Corey-Bakshi-Shibata reduction, phenolic oxidative cyclization, the intramolecular radical cyclization-benzylic oxidative cyclization sequence, and intramolecular [2 + 2] photocycloaddition. These key steps enabled enantioselective access with the longest linear sequence of 17 steps and 9% overall yield for (+)-ganocin A and with 16 steps and 9% overall yield for (-)-cohlearol B.

Total Synthesis of (-)-Lamellodysidine A via an Intramolecular Diels-Alder Reaction.

In this study, we achieved an eight-step enantioselective synthesis of (-)-lamellodysidine A, a structurally intriguing sesquiterpene natural product featuring a 5/5/6/6-fused tetracyclic skeleton that was obtained from the marine sponge . The key to the synthesis is a cascade reaction that includes an intramolecular Diels-Alder reaction. In addition, single-crystal X-ray crystallographic analysis of the synthetic (-)-lamellodysidine A clearly confirmed the proposed stereochemistry and absolute configuration.

Total Synthesis of Cochlearol B via Intramolecular [2+2] Photocycloaddition.

Herein, we describe the first total synthesis of cochlearol B, a meroterpenoid natural product featuring a 4/5/6/6/6-fused pentacyclic structure. Key steps, oxidative cyclization and subsequent intramolecular [2+2] photocycloaddition, which constructed the pentacyclic structure in highly stereoselective manner, allowed efficient access to cochlearol B with the longest linear sequence of 16 steps, and in 9 % overall yield. Single-crystal X-ray crystallographic analysis clearly confirmed the stereochemistry of cochlearol B.

Convergent total synthesis of corallocin A.

The first total synthesis of corallocin A is described herein. The Suzuki coupling reaction as a key step proceeded with high stereoselectivity and in good yield. Robust transformations, including Vilsmeier-Haack formylation and Wittig reaction, allowed for effective access to corallocin A.

Further investigation of the rapid-onset and short-duration action of the G protein-biased μ-ligand oliceridine.

TRV130 (oliceridine), a G protein-biased ligand for μ-opioid receptor, has recently been synthesized. It is considered to have strong antinociceptive effects and only minor adverse effects. However, whether or not oliceridine actually exhibits an ideal pharmacological profile as an analgesic has not yet been fully clarified in animal studies.

Diastereoselective Total Syntheses of (±)-Caseabalansin A and (±)-18-Epicaseabalansin A via Intramolecular Robinson-type Annulation.

Highly diastereoselective total syntheses of (±)-caseabalansin A (1) and (±)-18-epicaseabalansin A (2) are described in this paper. We revealed that the intramolecular Robinson-type annulation of an alkynone was effective in the stereocontrolled construction of the bicyclic skeleton of 1 and 2. Further transformation of the resulting enone, including diastereoselective reduction by LiAlH(OtBu) , hydroxy-group-directed hydrogenation, cyclization to form the cyclic acetal moiety, and introduction of a side chain by a C(sp )-C(sp ) Stille coupling reaction, resulted in the total syntheses of (±)-1 and (±)-2.

Facile Total Synthesis of (+)-Spinoxazine B.

Herein we describe a short total synthesis of (+)-spinoxazine B, which inhibits nitric oxide (NO) production in BV-2 microgrial cells. Spinoxazine B is the first example of a natural alkaloid containing an oxazinone-pyrrolidone nucleus, and it is expected to serve as a novel drug lead compound as well as a drug discovery scaffold.

Enantioselective, Protecting-Group-Free Total Synthesis of Boscartin F.

In this work, the protecting-group-free total synthesis and stereochemical assignment of (-)-boscartin F have been reported. The key steps, including Sharpless asymmetric epoxidation, I-mediated iodoetherification, aldol reaction, and ring-closing metathesis, allowed for rapid and highly stereoselective access to boscartin F. In addition, single-crystal X-ray crystallographic analysis of the semicarbazone derivative 22 confirmed the stereochemistry of boscartin F.

Usefulness for the combination of G-protein- and β-arrestin-biased ligands of μ-opioid receptors: Prevention of antinociceptive tolerance.

Background: µ-Opioid receptor internalization is considered to be critically linked to antinociceptive tolerance. Although µ-opioid receptor agonists have been administered simultaneously with other drugs to control pain, little information is available regarding opioid–opioid interactions. Therefore, the present study was designed to further investigate the utility of a new G protein-biased ligand for µ-opioid receptors, TRV130, which has an antinociceptive effect without β-arrestin-dependent µ-opioid receptor internalization, and its combination with fentanyl using µ-opioid receptor-expressing cells and mice.

Direct Catalytic Asymmetric Aldol Addition of an α-CF Amide to Arylglyoxal Hydrates.

Direct asymmetric aldol addition of an α-CF amide to arylglyoxal hydrates was promoted by a chiral catalyst comprising a soft Lewis acidic Cu(I), a chiral bisphosphine ligand, and DBU. The 7-azaindoline moiety of the amide facilitates its enolization and stabilizes the thus-generated Cu enolate, furnishing enantioenriched aldol adducts.

Iodoalkyne-Based Catalyst-Mediated Activation of Thioamides through Halogen Bonding.

Halogen bonding catalysis has recently gained increasing attention as a powerful tool to activate organic molecules. However, the variety of the catalyst structure has been quite limited so far. Herein, we report the first example of the use of an iodoalkyne as a halogen bond donor catalyst.

Direct aldol strategy in enantioselective total synthesis of thuggacin B.

An enantioselective total synthesis of thuggacin B, a natural product exhibiting antibiotic activity against Mycobacterium tuberculosis, is described. Asymmetric direct aldol reactions promoted by Cu and Zn catalysts play a pivotal role in constructing four stereogenic centers. The use of direct aldol reactions as the initial steps for the synthesis of two key fragments allowed the construction of the other stereogenic centers through chirality transfer.

Solvent-dependent self-discrimination of bis(2-hydroxyphenyl)diamides.

Solvent-dependent, self-discrimination of diamides is described. Mixing a solution of (R)-1a and (S)-1a, which are valine-derived, bis(2-hydroxyphenyl)diamide-bearing, multiple hydrogen-bonding modules, in dichloromethane immediately led to the formation of a thick suspension comprising a 1:1 heterochiral aggregate of 1a. The solubility of heterochiral 1a was substantially lower in halogenated solvents than in ethyl acetate.