Synthetic Approach toward Diverse Oxa-Cages via Olefin Metathesis.

This article demonstrates a late-stage modification of the cage propellanes that are transformed into intricate oxa-cycles via ring-rearrangement metathesis (RRM) and regioselective ring-closing metathesis (RCM) as crucial steps. In addition, we also report the extended pentacycloundecane (PCUD)-based oxa-cages involving the domino cycloetherification followed by olefin metathesis. These oxa-cages involve a domino sequence in which the PCUD core unit remains intact.

Molecular Acrobatics in Polycyclic Frames: Synthesis of "Kurmanediol" via Post-synthetic Modification of Cage Molecules by Olefinic Metathesis.

We report late-stage ring-opening metathesis (ROM), ring-rearrangement metathesis (RRM), and ring-closing metathesis (RCM) approaches to generate expanded pentacycloundecane (PCUD) cage derivatives. These higher-order intricate polycyclic cage systems are aesthetically pleasing and structurally intriguing. Their assembly maintains molecular symmetry during the entire synthetic sequence.

Late-stage Modification of Cage Diones by Tandem Metathesis.

Herein, we report the application of tandem ring-opening cross-metathesis (ROCM) and tandem ring-opening cross-metathesis followed by cross-metathesis (ROCM/CM) in highly strained diastereomeric heptacyclic cage diones (HCCD's) catalyzed by ruthenium catalysts. These caged diastereomeric compounds have a high degree of ring strain as well as steric congestion. Therefore, the present work related to ROCM is unique and intricate as compared to simple norbornene derivatives.

-(2a,2a ,3a,3a ,5a,6a)-2a-Allyl-2,4-di-chloro-2a,2a,3a,5a,6,6a-hexa-hydro-3a-3-oxadi-cyclo-penta-[,]penta-len-3a-ol.

The title racemic triquinane, CHClO, is composed of four five-membered rings, one of which is a tetra-hydro-furan ring to which an allyl group on one side and a hydroxyl group on the other side are attached. The core of the triquinane unit has a configuration. In the crystal, the mol-ecules are linked by pairwise O-H⋯O hydrogen bonds, generating inversion dimers featuring (8) loops.

An Intramolecular Cycloetherification of Unactivated Olefinic Substrates Bearing endo-Alcohol: Access to Diversely Alkylated Oxa-Cage Derivatives Useful for Olefin-Metathesis.

Herein, we report an efficient and rapid synthetic methodology to access diversely substituted oxa-cages from unactivated olefinic substrates derived from endo-norbornenes by employing Lewis acid- (BF  ⋅ OEt ) or base (NaH)-promoted intramolecular etherification. Although both BF  ⋅ OEt and NaH are found to be efficient for this transformation, slightly better yields and less reaction times are achieved with NaH/DMF (0.25-1 h at 100 °C) as compared to BF  ⋅ OEt /DCM (2-3 h at 0 °C to rt).

Design and synthesis of hetero-steroids via ring-closing metathesis: Biological studies towards in vitro anticancer activity.

Here, we report a synthetic approach to hetero-steroids and also studied their biological activities as anticancer agents. A novel class of oxacycles containing estrone moiety were synthesized in this report. Allyl ether derived from estrone underwent Claisen rearrangement (CR) and again O-allylation and subsequent ring-closure gave A-ring-furan and oxepine fused derivatives in high yields.

One-pot thiol-free synthetic approach to sulfides, and sulfoxides selectively.

A facile and efficient thiol-free one-pot method for direct synthesis of sulfides and sulfoxides under green conditions without using any metal catalyst is reported. For this purpose, we used benzyl bromides as starting materials in the presence of potassium thioacetate (PTA) and Oxone® which are low-cost, and readily accessible chemicals. This method is highly compatible with a variety of functional groups and delivered a series of sulfides, bis-sulfides, and sulfoxides in good yields.

Annulation Tactics of cis-syn-cis Triquinanes by Allylsilanes: Application of Hosomi-Sakurai Reaction Conditions.

A stereoselective [3+2] cycloaddition approach to functionalized pentaquinanes starting from cis-syn-cis triquinanes, derived from Cookson's diones, is reported. This transformation involves generation of six new stereocenters in a single step leading to cis-anti-cis-syn-cis-anti-cis polyquinane systems. Our method prevents transannular cyclizations which are prevalent in these moieties.

Synthesis of mixed musks Eschenmoser-Tanabe fragmentation, enyne metathesis and Diels-Alder reaction as key steps.

Musk analogues containing different macrocyclic ring systems as well as different annulated ring systems were synthesised by a simple and useful strategy. This strategy includes Eschenmoser-Tanabe fragmentation, enyne metathesis and Diels-Alder reaction as key steps. Starting from easily available () macrocyclic ketones, ( + 3) macrocyclic systems were assembled using the basic organic reactions.

Modular Approach to Benzofurans, 2H-Chromenes and Benzoxepines via Claisen Rearrangement and Ring-Closing Metathesis: Access to Phenylpropanoids.

Benzofurans, 2H-chromenes and benzoxepines are key structural elements present in several natural products and pharmaceuticals. Here, we describe an easy-to-execute strategy for the synthesis of benzofurans, 2H-chromenes and benzoxepines, by employing Claisen rearrangement and ring-closing metathesis as key steps. A variety of phenols were converted into useful oxacycles in good to excellent yields.

A Modular Approach to Angularly Fused Polyquinanes via Ring-Rearrangement Metathesis: Synthetic Access to Cameroonanol Analogues and the Basic Core of Subergorgic Acid and Crinipellin.

We describe a modular approach to angularly fused polyquinanes that are core units of many natural products such as cameroonanol, subergorgic acid, and crinepellin, etc. in excellent yields by employing atom-economic ring-rearrangement metathesis as a key step. Our work highlights, the synthesis of cameroonanol analogues - and their ester derivatives by using the stereoselective reduction of the carbonyl group by using DIBAL-H- and DCC-mediated coupling as the key reactions.

Design, Synthesis and Late-Stage Modification of Indane-Based Peptides via [2+2+2] Cyclotrimerization.

Here, we prepared several dipeptides containing 2-aminoindane-2-carboxylic acid (Aic) and carried out further synthetic transformations. Synthesis and purification of modified peptides by using [2+2+2] cyclotrimerization is a challenging task. We are able to modify the unusual amino acids and peptide derivatives by late-stage incorporation of benzylhalo functionality.

5-[(1,3-Dimethyl-5-oxo-2-sulfanylideneimidazolidin-4-yl-idene)amino]-2-methyl-isoindoline-1,3-dione.

The title ,-di-methyl-thio-hydantoin containing an -methyl-ated pthalimide group, CHNOS, arose from an unexpected reaction in a deep eutectic di-methyl-thio-urea-tartaric acid solvent system. The mean planes of the ring systems are twisted at an angle of 73.84 (17)°.

2,3-Di-hydro-1-cyclo-penta-[]naphthalene-4,9-dione.

The title compound, CHO, crystallizes with two almost planar mol-ecules in the asymmetric unit. In the crystal, slipped π-π stacking inter-actions help to establish the packing with the shortest centroid-centroid separation being 3.8195 (18) Å.

()-3-Thia-1,5(1,3)-dibenzena-cyclo-undeca-phan-8-ene-6,11-dione 3,3-dioxide.

The molecular structure of the title cyclophane, CHOS, has two benzyl groups, a sulfone group, and two carbonyl groups adjacent to a double bond. The phenyl rings do not show intra-molecular stacking.

7-Meth-oxy-penta-cyclo-[5.4.0.0.0.0]undec-ane-8,11-dione.

The structure of 7-meth-oxy-penta-cyclo-[5.4.0.

A new skeletal rearrangement of 1,7-dimethyl Cookson's cage dione catalyzed by a Lewis acid.

A methyl-substituted polycyclic cage dione containing the PCUD framework has undergone an unprecedented ring rearrangement approach. Here, the PCUD framework with the aid of a Lewis acid such as BF3·MeOH gave unusual fragmentation products. Two new products were isolated via the skeletal rearrangement process involving carbocation mediated intermediates.

Diversity-Oriented Approaches to Polycycles and Heterocycles via Enyne Metathesis and Diels-Alder Reaction as Key Steps.

Enyne metathesis (EM) has extensively been used to prepare diverse polycycles and heterocycles. EM in combination with Diels-Alder (DA) reaction has been used to prepare densely functionalized targets in a simple manner. In this mini-review, we discuss the various diversity-oriented approaches reported from our laboratory to prepare a variety of organic frameworks by a synergistic combination of EM and DA reactions.

Diversity-oriented synthesis of spirothiazolidinediones and their biological evaluation.

We report a new synthetic approach to assemble spirothiazolidinediones via a [2 + 2 + 2] cyclotrimerization reaction and the derivatives were further functionalized through DA chemistry and click reaction. Using flow cytometry, it was shown for the first time that the new benzyl alcohol derivatives of thiazolidine-2,4-dione generated here are efficient apoptosis inducers in the HeLa, Hek293, U937, Jurkat, and K562 cell lines.

Synthetic Strategies to Diverse Polyquinanes via Olefin Metathesis: Access to the Basic Core of Crinipellin, Presilphiperfolanol, and Cucumin.

A rapid and useful synthetic approach to various polyquinane-based natural products was accomplished efficiently by employing ring-rearrangement metathesis and ring-closing metathesis as key steps. Here, we report the synthesis of stereochemically well-defined triquinanes (, ), tetraquinanes (, ), a novel pentaquinane , and fused [5-5-5-6] tetracyclic systems (, ) that are present in crinipellin, presilphiperfolanol, cucumin, etc. Hence, the current strategy may be suitable for the synthesis of various complex natural and unnatural cyclopentanoid targets.

Synthetic Approach to the ABCD Ring System of Anticancer Agent Fredericamycin A via Claisen Rearrangement and Ring-Closing Metathesis as Key Steps.

A new synthetic strategy to the ABCD ring system of the anticancer agent fredericamycin A (NSC-305263) was realized by the Diels-Alder reaction and olefin metathesis as key steps. The tactics developed here for the construction of the ABCD ring system also involve double Claisen rearrangement followed by a retro-Diels-Alder reaction and ring-closing metathesis. The metathesis approach performs a key role in the construction of A and D rings of the ABCD core unit.

Development of New Synthetic Strategies, Tactics and their Applications.

This account covers our work related to the development of various synthetic methodologies since 1994. We summarized our strategies and their application to design various functional molecules. In this regard, we also report the utility of our methodologies in others research work.

Multicomponent Approach to Hydantoins and Thiohydantoins Involving a Deep Eutectic Solvent.

We report an efficient synthetic strategy to diverse hydantoins and thiohydantoins involving a three-component reaction with the aid of deep eutectic solvent. Here, N,N'-dimethyl urea and N,N'-dimethyl thiourea play a dual role as reactant and reaction medium along with l-(+)-tartaric acid. The three-component reaction provides an easy access to 5-amino-1,3-dialkyl-substituted hydantoins and thiohydantoins in good yields.

Synthesis of -symmetric star-shaped molecules containing α-amino acids and dipeptides via Negishi coupling as a key step.

We demonstrate a new synthetic strategy toward star-shaped -symmetric molecules containing α-amino acid (AAA) derivatives and dipeptides. In this regard, trimerization and Negishi cross-coupling reactions are used as the key steps starting from readily available 4'-iodoacetophenone and L-serine. These -symmetric molecules containing AAA moieties are useful to design new ligands suitable for asymmetric synthesis and peptide dendrimers.

Synthetic Approaches to Star-Shaped Molecules with 1,3,5-Trisubstituted Aromatic Cores.

Herein, we summarize the synthetic approaches that have been developed for the synthesis of star-shaped molecules. Typically, to design such highly functionalized molecules, simple building blocks are first assembled through trimerization reactions, starting from commercially available starting materials. Then, these building blocks are synthetically manipulated to generate extended star-shaped molecules.