Synthesis of phosphine oxide based amphiphilic molecules ring-opening Wittig olefination of a macrocyclic phosphoranylidene and their property study as non-ionic surfactants.

A novel ring-opening Wittig olefination approach was developed for the synthesis of amphiphilic phosphine oxides (PO) as non-ionic surfactants. The approach concurrently introduces the crucial functional groups (lipophilic chain and phosphine oxide moiety) present in the known PO surfactants and additional hydrophilic group (, ethylene glycol units) in one step Wittig olefination of a macrocyclic phosphoranylidene. A series of novel PO compounds were obtained from a variety of aldehydes and selected compounds were examined for their physiochemical properties (surface tension, critical micelle concentration and interfacial tension) and also for their abilities to form emulsions as non-ionic surfactants.

An intramolecular tryptophan-condensation approach for peptide stapling.

Stapled peptides are gaining tremendous interest as next-generation therapeutic agents to target protein-protein interactions. Herein, we report an intramolecular peptide stapling method which links two tryptophan residues at the C2 position of the indole moieties via acid-mediated condensation with an aldehyde.

Preparation and characterization of quercetin/dietary fiber nanoformulations.

Quercetin is well known for its beneficial health effects on the human body. However, the slow dissolution rate leading to poor bioavailability constitutes a barrier to being further developed for nutritional products. In this work, quercetin was co-precipitated with dietary fibers into a fast-dissolving nanoformulation via antisolvent precipitation, followed by spray drying.

Hot-melt extrusion microencapsulation of quercetin for taste-masking.

Besides its poor dissolution rate, the bitterness of quercetin also poses a challenge for further development. Using carnauba wax, shellac or zein as the shell-forming excipient, this work aimed to microencapsulate quercetin by hot-melt extrusion for taste-masking. In comparison with non-encapsulated quercetin, the microencapsulated powders exhibited significantly reduced dissolution in the simulated salivary pH 6.

Anti-proliferative activity of the NPM1 interacting natural product avrainvillamide in acute myeloid leukemia.

Mutated nucleophosmin 1 (NPM1) acts as a proto-oncogene and is present in ~30% of patients with acute myeloid leukemia (AML). Here we examined the in vitro and in vivo anti-leukemic activity of the NPM1 and chromosome region maintenance 1 homolog (CRM1) interacting natural product avrainvillamide (AVA) and a fully syntetic AVA analog. The NPM1-mutated cell line OCI-AML3 and normal karyotype primary AML cells with NPM1 mutations were significantly more sensitive towards AVA than cells expressing wild-type (wt) NPM1.

Directed Evolution of a Fluorinase for Improved Fluorination Efficiency with a Non-native Substrate.

Fluorinases offer an environmentally friendly alternative for selective fluorination under mild conditions. However, their diversity is limited in nature and they have yet to be engineered through directed evolution. Herein, we report the directed evolution of the fluorinase FlA1 for improved conversion of the non-native substrate 5'-chloro-5'-deoxyadenosine (5'-ClDA) into 5'-fluoro-5'-deoxyadenosine (5'-FDA).

Interactions of the natural product (+)-avrainvillamide with nucleophosmin and exportin-1 Mediate the cellular localization of nucleophosmin and its AML-associated mutants.

Nucleophosmin (NPM1) is a multifunctional phosphoprotein localized predominantly within the nucleoli of eukaryotic cells. Mutations within its C-terminal domain are frequently observed in patients with acute myeloid leukemia (AML), are thought to play a key role in the initiation of the disease, and result in aberrant, cytoplasmic localization of the mutant protein. We have previously shown that the electrophilic antiproliferative natural product (+)-avrainvillamide (1) binds to proteins, including nucleophosmin, by S-alkylation of cysteine residues.

Stabilized Wittig olefination for bioconjugation.

Stabilized Wittig olefination holds great potential as a bioconjugation reaction. We demonstrate that the reaction of stabilized phosphorus ylides (or phosphonium salts) with aryl aldehydes is sufficiently robust to be used for live cell affinity isolation and fluorescence tagging of a protein, FKBP12.

Lagunamide C, a cytotoxic cyclodepsipeptide from the marine cyanobacterium Lyngbya majuscula.

Lagunamide C (1) is a cytotoxic cyclodepsipeptide isolated from the marine cyanobacterium, Lyngbya majuscula, from the western lagoon of Pulau Hantu Besar, Singapore. The complete structural characterization of the molecule was achieved by extensive NMR spectroscopic analysis as well as chemical manipulations. Several methods, including the advanced Marfey's method, a modified method based on derivatization with Mosher's reagents and analysis using LC-MS, and the use of (3)J(H-H) coupling constant values, were utilized for the determination of its absolute configuration.

Formal synthesis of (+)-SCH 351448: the Prins cyclization approach.

The formal synthesis of (+)-SCH 351448 has been accomplished with the catalytic Prins cyclization strategy, yielding the monomeric unit as a single isomer.

Stannane-free chemoselective hydrodehalogenation of 4-halotetrahydropyrans: scope and application to natural product synthesis.

A stannane-free hydrodehalogenation of 4-halotetrahydropyran under very mild conditions has been developed. This methodology allows selective one-pot dehalogenation and/or debenzylation depending on the type of halide-substrate used. The applicability of this methodology is well demonstrated in the synthesis of a key intermediate toward the enantioselective synthesis of (+)-SCH 351448.

Prins cyclizations in silyl additives with suppression of epimerization: versatile tool in the synthesis of the tetrahydropyran backbone of natural products.

[reactions: see text] A catalytic Prins cyclization reaction has been developed. The involvement of trimethylsilyl halides offers a versatile route to the formation of cis-4-halo-2,6-disubstituted tetrahydropyran rings. The problem of epimerization in Prins cyclization has also been addressed in the total synthesis of (-)-centrolobine using this methodology.