82263-48-7

Upstream product

• 99267-80-8 (4R,5R)-2-((1R,2R)-2-Phenyl-cyclopropyl)-[1,3]dioxolane-4,5-dicarboxylic acid diisopropyl ester 
• 14371-10-9 (E)-3-phenylpropenal 
• 1062310-21-7 1,2-O-isopropylidene-3,5-O-[(1S,2R,3R)-(2-phenylcyclopropyl)methylidene]-α-D-xylofuranose 
• 110659-58-0 (1R,2R)-1-hydroxymethyl-2-phenylcyclopropane 
• 110659-58-0 (1S,2S)-trans-1-(hydroxymethyl)-2-phenylcyclopropane 
• 936-98-1 ((S)-2-Phenyl-cyclopropyl)-methanol 
• 23020-15-7 (1S,2S)-2-phenylcyclopropane-1-carboxylic acid 
• 1394897-70-1 (1R,1'S,2'S)-1-(2-phenylcyclopropyl)ethane-1,2-diol 
• 1394897-58-5 C₂₀H₂₄O₂S 
• 37107-48-5 (1R,2R)-trans-2-phenylcyclopropane-1-carboxyl chloride 
• 1421259-31-5 C₂₇H₂₉N 
• 107804-91-1 ((1S,2R)-2-Dimethoxymethyl-cyclopropyl)-benzene 
• 33732-62-6 2-phenyl-2,3-dihydrofuran 
• 936-98-1 rac-((1S,2R)-2-phenylcyclopropyl)methanol 

Downstream Products

• 3471-10-1 (1R,2R)-trans-2-phenyl-1-cyclopropanecarboxylic acid 
• 110659-58-0 (1R,2R)-1-hydroxymethyl-2-phenylcyclopropane 
• 1188287-58-2 C₁₇H₁₄OS 
• 1188287-59-3 C₁₈H₁₆OS 
• 679429-87-9 1-((1S,2S)-2-Phenyl-cyclopropyl)-but-3-en-1-one 
• 625455-49-4 (1R,1’S,2’S)-1-(2-phenylcyclopropyl)but-3-en-1-ol 
• 625455-51-8 (6R,1'S,2'S)-6-(2'-phenylcyclopropyl)-5,6-dihydro-2H-pyran-2-one 
• 625455-50-7 Acrylic acid (R)-1-((1S,2S)-2-phenyl-cyclopropyl)-but-3-enyl ester 
• 22467-91-0 cis-1-(trans-β-Ethoxycarbonylvinyl)-2-phenylcyclopropan 
• 17955-08-7 cis-2-Phenyl-vinyl-cyclopropan 

Relevant academic research and scientific papers

Skeletally Tunable Seven-Membered-Ring Fused Pyrroles

We describe a copper-mediated method that enables the synthesis of seven-membered-ring fused pyrroles (7-mrFPs). The protocol proceeds via an in situ spiro-intermediate ring expansion and tolerates a library of 7-mrFP derivatives with a broad range of functional groups in a simple step with tangible parameters and substrate adaptations. These rare 7-mrFPs are now accessible on a millimolar scale, and selected examples exhibit high antioxidant activity.

Donor-Acceptor Bicyclopropyls as 1,6-Zwitterionic Intermediates: Synthesis and Reactions with 4-Phenyl-1,2,4-triazoline-3,5-dione and Terminal Acetylenes

The bicyclopropyl system activated by incorporation of donor and acceptor groups in the presence of Lewis acids was used as a synthetic equivalent of 1,6-zwitterions. Opening of both cyclopropane rings in 2′-aryl-1,1′-bicyclopropyl-2,2-dicarboxylates (D-A bicyclopropyl, ABCDs) in the presence of GaI3 + Bu4N+GaI4- results in 5-iodo-5-arylpent-2-enylmalonates as products of HI formal 1,6-addition to the bicyclopropyl system. The use of GaCl3 or GaBr3 as a Lewis acid and terminal aryl or alkyl acetylenes as 1,6-zwitterion interceptors allows the alkyl substituent to be grown to give the corresponding acyclic 7-chloro(bromo)-hepta-2,6-dienylmalonates. The reaction of ABCDs with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) catalyzed by Yb(OTf)3 also results in the opening of both cyclopropane rings. The reaction products are tetrahydropyridazine derivatives - (7,9-dioxo-1,6,8-triazabicyclo[4.3.0]non-3-en-2-ylmethyl)malonates - containing one more PTAD moiety in the malonyl group.

Visible-Light Controlled Divergent Catalysis Using a Bench-Stable Cobalt(I) Hydride Complex

While the use of visible light in conjunction with transition metal catalysis offers powerful opportunities to switch between on/-off states of catalytic activity, the next frontier would be the ability to switch the actual function of the catalyst and resulting products. Here we report such an example of multi-dimensional catalysis. Featuring an easily prepared, bench-stable cobalt(I) hydride complex in conjunction with pinacolborane, we can switch the reaction outcome between two widely employed transformations, olefin migration and hydroboration, with visible light as the trigger.

5,6,7,8-Tetrahydro-1,6-naphthyridine Derivatives as Potent HIV-1-Integrase-Allosteric-Site Inhibitors

A series of 5,6,7,8-tetrahydro-1,6-naphthyridine derivatives targeting the allosteric lens-epithelium-derived-growth-factor-p75 (LEDGF/p75)-binding site on HIV-1 integrase, an attractive target for antiviral chemotherapy, was prepared and screened for activity against HIV-1 infection in cell culture. Small molecules that bind within the LEDGF/p75-binding site promote aberrant multimerization of the integrase enzyme and are of significant interest as HIV-1-replication inhibitors. Structure-activity-relationship studies and rat pharmacokinetic studies of lead compounds are presented.

Lewis Acid Catalyzed Annulation of Cyclopropane Carbaldehydes and Aryl Hydrazines: Construction of Tetrahydropyridazines and Application Toward a One-Pot Synthesis of Hexahydropyrrolo[1,2- b]pyridazines

In this report, a facile synthesis of tetrahydropyridazines via a Lewis acid catalyzed annulation reaction of cyclopropane carbaldehydes and aryl hydrazines has been demonstrated. Moreover, the generated tetrahydropyridazine further participated in a cycloaddition reaction with donor-acceptor cyclopropanes to furnish hexahydropyrrolo[1,2-b]pyridazines. We also performed these two steps in one pot in a consecutive manner. In addition, a monodecarboxylation reaction of hexahydropyrrolo[1,2-b]pyridazine was achieved with a good yield.

Asymmetric Reductive Carbocyclization Using Engineered Ene Reductases

Ene reductases from the Old Yellow Enzyme (OYE) family reduce the C=C double bond in α,β-unsaturated compounds bearing an electron-withdrawing group, for example, a carbonyl group. This asymmetric reduction has been exploited for biocatalysis. Going beyond its canonical function, we show that members of this enzyme family can also catalyze the formation of C?C bonds. α,β-Unsaturated aldehydes and ketones containing an additional electrophilic group undergo reductive cyclization. Mechanistically, the two-electron-reduced enzyme cofactor FMN delivers a hydride to generate an enolate intermediate, which reacts with the internal electrophile. Single-site replacement of a crucial Tyr residue with a non-protic Phe or Trp favored the cyclization over the natural reduction reaction. The new transformation enabled the enantioselective synthesis of chiral cyclopropanes in up to >99 % ee.

Generation of Phosphoranyl Radicals via Photoredox Catalysis Enables Voltage-Independent Activation of Strong C-O Bonds

Despite the prevalence of alcohols and carboxylic acids as functional groups in organic molecules and the potential to serve as radical precursors, C-O bonds remain difficult to activate. We report a synthetic strategy for direct access to both alkyl and acyl radicals from these ubiquitous functional groups via photoredox catalysis. This method exploits the unique reactivity of phosphoranyl radicals, generated from a polar/SET crossover between a phosphine radical cation and an oxygen-centered nucleophile. We show the desired reactivity in the reduction of benzylic alcohols to the corresponding benzyl radicals with terminal H atom trapping to afford the deoxygenated products. Using the same method, we demonstrate access to synthetically versatile acyl radicals, which enables the reduction of aromatic and aliphatic carboxylic acids to the corresponding aldehydes with exceptional chemoselectivity. This protocol also transforms carboxylic acids to heterocycles and cyclic ketones via intramolecular acyl radical cyclizations to forge C-O, C-N, and C-C bonds in a single step.

Synthesis and cytotoxic activities of goniothalamins and derivatives

Substituted goniothalamins containing cyclopropane-groups were efficiently prepared in high yields and good selectivity. Antiproliferative activity was measured on three human cancer cell lines (A549, MCF-7, HBL-100), to show which of the structural elements of goniothalamins is mandatory for cytotoxicity. We found that the configuration of the stereogenic centre of the δ-lactone plays an important role for cytotoxicity. In our studies only (R)-configured goniothalamins showed antiproliferative activity, whereby (R)-configuration accords to natural goniothalamin (R)-1. Additionally, the δ-lactone needs to be unsaturated whereas our results show that the vinylic double bond is not mandatory for cytotoxicity. Furthermore, with a two-fold in vitro and in vivo strategy, we determined the inhibitory effect of the compounds to the yeast protein Pdr5. Here, we clearly demonstrate that the configuration seems to be of minor influence, only, while the nature of the substituent of the phenyl ring is of prime importance.

Characterization of Carboxylic Acid Reductases as Enzymes in the Toolbox for Synthetic Chemistry

Carboxylic acid reductase enzymes (CARs) meet the demand in synthetic chemistry for a green and regiospecific route to aldehydes from their respective carboxylic acids. However, relatively few of these enzymes have been characterized. A sequence alignment with members of the ANL (Acyl-CoA synthetase/ NRPS adenylation domain/Luciferase) superfamily of enzymes shed light on CAR functional dynamics. Four unstudied enzymes were selected by using a phylogenetic analysis of known and hypothetical CARs, and for the first time, a thorough biochemical characterization was performed. Kinetic analysis of these enzymes with various substrates shows that they have a broad but similar substrate specificity. Electron-rich acids are favored, which suggests that the first step in the proposed reaction mechanism, attack by the carboxylate on the α-phosphate of adenosine triphosphate (ATP), is the step that determines the substrate specificity and reaction kinetics. The effects of pH and temperature provide a clear operational window for the use of these CARs, whereas an investigation of product inhibition by NADP+, adenosine monophosphate, and pyrophosphate indicates that the binding of substrates at the adenylation domain is ordered with ATP binding first. This study consolidates CARs as important and exciting enzymes in the toolbox for sustainable chemistry and provides specifications for their use as a biocatalyst.

Stereoconvergent [1,2]- and [1,4]-wittig rearrangements of 2-silyl-6-aryl-5,6-dihydropyrans: A tale of steric Vs electronic regiocontrol of divergent pathways

The regiodivergent ring contraction of diastereomeric 2-silyl-5,6-dihydro-6-aryl-(2H)-pyrans via [1,2]- and [1,4]-Wittig rearrangements to the corresponding α-silylcyclopentenols or (α-cyclopropyl)acylsilanes favor the [1,4]-pathway by ortho and para directing groups in the aromatic appendage and/or by sterically demanding silyl groups. The [1,2]-pathway is dominant with meta directing or electron-poor aromatic moieties. Exclusive [1,2]-Wittig rearrangements are observed when olefin substituents proximal to the silyl are present. cis and trans diastereomers exhibit different reactivities, but converge to a single [1,2]- or [1,4]-Wittig product with high diastereoselectivity and yield.