185986-76-9

Upstream product

• 540-88-5 acetic acid tert-butyl ester 
• 106-96-7 propargyl bromide 
• 507-19-7 t-butyl bromide 
• 6089-09-4 4-pentynoic acid 
• 24424-99-5 di-tert-butyl dicarbonate 
• 75-65-0 tert-butyl alcohol 

Downstream Products

• 6089-09-4 4-pentynoic acid 
• 1027569-16-9 C₁₉H₂₉NO₄ 

Relevant academic research and scientific papers

Experimental and Computational Study on the Intramolecular Hydrogen Atom Transfer Reactions of Maleimide-Based Enediynes after Cycloaromatization

The follow-up reaction pathways of the diradical species formed from cycloaromatization of enediynes or enyne-allenes determine their ability of H-abstraction from DNA, significantly affecting their biological activity performance. To gain a deeper unders

Ruthenium-catalyzed alder ene type reactions. A formal synthesis of alternaric acid

Alternaric acid, a nanomolar fungal germination inhibitor, is typified by a 1,4-diene, consisting of a terminal methylene and an (E)-l,2- disubstituted alkene. A new strategy for the synthesis of natural products containing such functionality stems from the development of a ruthenium- catalyzed addition of terminal alkenes with terminal alkynes. The alkyne substrate, 4-pentynoic acid, is commercially available or can be prepared in two steps by alkylation of tert-butyl acetate. The alkene substrate is prepared from commercially available (S)-2-methyl-l-butanol. This synthesis involves formation of a geometically defined trisubstituted alkene by involving Pd-catalyzed cross-coupling and asymmetric dihydroxylation. The ruthenium-catalyzed coupling proceeds best in the absence of alcohol protecting groups to maximize regioselectivity. The examples of this addition illustrated herein help elucidate some of the important factors controlling regioselectivity. They also illustrate the excellent chemoselectivity. The acyclic unit of alternaric acid, which is simply coupled to a dihydropyrone fragment to complete the synthesis, is available in only 11 steps and 27% overall yield compared to the one extant synthesis also starting from (S)-2- methyl-1-butanol which proceeds in 26 steps and 0.003% overall yield. This new reaction provides a powerful tool in streamlining this synthesis and should prove more generally useful.

Migratory Hydrogenation of Terminal Alkynes by Base/Cobalt Relay Catalysis

Migratory functionalization of alkenes has emerged as a powerful strategy to achieve functionalization at a distal position to the original reactive site on a hydrocarbon chain. However, an analogous protocol for alkyne substrates is yet to be developed. Herein, a base and cobalt relay catalytic process for the selective synthesis of (Z)-2-alkenes and conjugated E alkenes by migratory hydrogenation of terminal alkynes is disclosed. Mechanistic studies support a relay catalytic process involving a sequential base-catalyzed isomerization of terminal alkynes and cobalt-catalyzed hydrogenation of either 2-alkynes or conjugated diene intermediates. Notably, this practical non-noble metal catalytic system enables efficient control of the chemo-, regio-, and stereoselectivity of this transformation.

Stepwise triple-click functionalization of synthetic peptides

The increasing popularity of peptides as promising molecular scaffolds for biomedical applications and as valuable biochemical probes makes new methods allowing for their modification highly desirable. We describe herein an optimized protocol based on a sequence of CuAAC click reactions and selective deprotection steps, which leads to an efficient multi-functionalization of synthetic peptides. The methodology has been successfully applied to the construction of defined heteroglycopeptides and fluorophore-quencher-containing probes for proteases. The developed chemistry thus represents an important addition to the available toolbox of methods enabling efficient postsynthetic modification of peptides. The commercial availability of numerous azide probes further greatly extends the application potential of the described methodology.

Stereospecific Allylic Functionalization: The Reactions of Allylboronate Complexes with Electrophiles

Allylboronic esters react readily with carbonyls and imines (π-electrophiles), but are unreactive toward a range of other electrophiles. By addition of an aryllithium, the corresponding allylboronate complexes display enhanced nucleophilicity, enabling addition to a range of electrophiles (tropylium, benzodithiolylium, activated pyridines, Eschenmoser's salt, Togni's reagent, Selectfluor, diisopropyl azodicarboxylate (DIAD), MeSX) in high regio- and stereocontrol. This protocol provides access to key new functionalities, including quaternary stereogenic centers bearing moieties such as fluorine and the trifluoromethyl group. The allylboronate complexes were determined to be 7 to 10 orders of magnitude more reactive than the parent boronic ester.

TRIAZOLE-ISOXAZOLE COMPOUND AND MEDICAL USE THEREOF

A compound represented by Formula [I]: or pharmaceutically acceptable salt thereof, wherein each symbol is as defined in the description.

Molecular construction of HIV-gp120 discontinuous epitope mimics by assembly of cyclic peptides on an orthogonal alkyne functionalized TAC-scaffold

Mimics of discontinuous epitopes of for example bacterial or viral proteins may have considerable potential for the development of synthetic vaccines, especially if conserved epitopes can be mimicked. However, due to the structural complexity and size of discontinuous epitopes molecular construction of these mimics remains challeging. We present here a convergent route for the assembly of discontinuous epitope mimics by successive azide alkyne cycloaddition on an orthogonal alkyne functionalized scaffold. Here the synthesis of mimics of the HIV gp120 discontinuous epitope that interacts with the CD4 receptor is described. The resulting protein mimics are capable of inhibition of the gp120-CD4 interaction. The route is convergent, robust and should be applicable to other discontinuous epitopes.

Asymmetric PPCys: Strongly fluorescing NIR labels

By a stepwise synthesis strategy biofunctionalized Pyrrolopyrrole Cyanines (PPCy) with an asymmetric substitution pattern were obtained. These exhibit extremely strong and narrowband NIR absorption and fluorescence. Internalization of a peptide bound PPCy is demonstrated using live cell microscopy.

Synthesis of 2-(4-carboxybutenyl)- and 2-(4-carboxybutynyl)-cyclopentene-1-carboxamides

Syntheses of 2-(4-carboxybut-1-enyl/4-carboxypent-1-ynyl)cyclopentene-1-carboxamides, compounds designed to mimic the phosphoSer-Pro dipeptide motif (the recognition sequence for the prolyl cis-trans isomerase Pin1), have been developed. Stille, Sonogashira and Suzuki couplings were envisaged to join the pentynoic and pentenoic acid side chains to the 2-position of cyclopentene-1-carboxylate esters. The ring- and side-chain carboxylic acids required orthogonal protection for later attachment of a Ph-NH(4-nitrophenyl) unit to the cyclopentene-1-carbonyl. The cyclopentenecarboxylates were unmasked and standard PyBOP peptide coupling afforded the target compounds. Comparisons of two routes using But and Me esters are reported.

FUNGAL CELL WALL SYNTHESIS GENE

A reporter system reflecting the transport process that transports GPI-anchored proteins to the cell wall was constructed and compounds inhibiting this process were discovered. Further, genes conferring resistance to the above compounds were identified and methods of screening for compounds that inhibit the activity of the proteins encoded by these genes were developed.Therefore, through the novel compounds, the present invention showed that antifungal agents having a novel mechanism, i.e. inhibiting the process that transports GPI-anchored proteins to the cell wall, could be achieved.