ABSTRACT
A general method for synthesizing optically active, primary, secondary, and tertiary organofluorides was developed. This chiral pool synthesis utilized the skeleton of arabinose to generate diastereomerically pure 2-oxazolidinone-fused aziridines, which underwent ring opening with a fluoride anion. The adducts, polyoxygenated organofluorides, were useful precursors to various fluorinated compounds, such as fluorinated amino acids.
Subject(s)
Aziridines , Oxazolidinones , Molecular Structure , Aziridines/chemistry , Stereoisomerism , Amines/chemistryABSTRACT
Kijanose is one of the most highly functionalized deoxysugars found in nature and a challenging synthetic target. We found that the ring opening of trisubstituted, 2-oxazolidinone-fused aziridines is regio- and stereoselective, and the azide adduct has the same stereochemistry as that of kijanose after converting the azido to a nitro group. Therefore, both α- and ß-methyl l-kijanosides were prepared from ethyl l-lactate in 14% total yield.
ABSTRACT
The total synthesis of (-)-antrocin and its enantiomer are presented. Antrocin (-)-1 is an important natural product which acts as an antiproliferative agent in a metastatic breast cancer cell line (IC50: 0.6 µM). The key features of this synthesis are: (a) selective anti-addition of trimethylsilyl cyanide (TMSCN) to α,ß-unsaturated ketone; (b) resolution of (±)-7 using chiral auxiliary L-dimethyl tartrate through formation of cyclic ketal diastereomers followed by simple column chromatography separation and acid hydrolysis; (c) substrate-controlled stereoselective aldol condensation of (+)-12 with monomeric formaldehyde and pyridinium chlorochromate (PCC) oxidation for synthesis of essential lactone core in (-)-14; and (d) non-basic Lombardo olefination of the carbonyl at the final step to yield (-)-antrocin. In addition, (+)-9 cyclic ketal diastereomer was converted to (+)-antrocin with similar reaction sequences.
Subject(s)
Biological Products/chemical synthesis , Breast Neoplasms/drug therapy , Cell Proliferation/drug effects , Lactones/chemical synthesis , Sesquiterpenes/chemical synthesis , Biological Products/chemistry , Biological Products/pharmacology , Breast Neoplasms/pathology , Cell Line, Tumor , Cyanides/chemical synthesis , Cyanides/chemistry , Female , Humans , Lactones/chemistry , Lactones/pharmacology , Neoplasm Metastasis , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , Stereoisomerism , Tartrates/chemical synthesis , Tartrates/chemistry , Trimethylsilyl Compounds/chemical synthesis , Trimethylsilyl Compounds/chemistryABSTRACT
Radical reduction of alkyl halides and aerobic oxidation of alkyl aromatics are reported using water-soluble container compounds (1 and 2). The reductions involve α,ω-dihalides (4-8 and 10) with radical initiators in cavitand hosts with varied binding affinities. Product distributions lead to general guidelines for the use of dynamic supramolecular systems with fast reactions. The binding of guest substrates in the hosts must show high affinities (Ka > 103 M-1) to ensure that the reactions take place under confinement in the containers.
ABSTRACT
Host-guest complexation of long chain α,ω-dibromides was evaluated in deep water-soluble cavitands 1 and 2. The bound dibromides (C7-C12) tumble rapidly on the NMR timescale and averaged signals were observed. The complexation allows mono hydrolysis of dibromides in aqueous solution. The arrangement of the products in the host-guest complex was fixed in an unsymmetrical manner that protects the guest from further reaction. Up to 93% yields of the mono-alcohols were obtained. The α,ω-dibromides formed a capsule with cavitand 2 and remained unreactive to hydrolysis.
ABSTRACT
Antrodia camphorata is an expensive mushroom that grows on the inner cavity of an endangered native tree of Taiwan namely Cinnamomum kanehirai Hayata. It is used as a traditional medicine in Taiwan and has several health benefits including free radical scavenging, anti-inflammatory, antimicrobial, hepatoprotective, neuroprotective, antidiabetic, and free radical-induced DNA damage protecting activities. Antroquinonol is a tetrahydro ubiquinone derivative found predominately in the mycelium of Antrodia camphorata, and is characterized by numerous biological and pharmacological activities. Several studies have revealed potential anticancer effects of antroquinonol in various carcinogenic models. Moreover, a phase II clinical trial is ongoing in the US and Taiwan to treat the lung cancer patients with this active compound. The present review aims at depicting a detailed view of the synthetic procedures of antroquinonol as well as deciphering its potential health benefits with a special emphasis on anticancer properties.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Antrodia/chemistry , Lung Neoplasms/drug therapy , Ubiquinone/analogs & derivatives , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Proliferation/drug effects , DNA Damage , Humans , Lung Neoplasms/pathology , Ubiquinone/chemistry , Ubiquinone/isolation & purification , Ubiquinone/pharmacologyABSTRACT
Cyclopropanation using dimethylsulfoxonium methylide (Corey-Chaykovsky reaction) was examined with a series of linear α,ß-unsaturated ketones, and the results showed that the major trajectory for the addition of the sulfur ylide to the enones is anti, related to the γ-substituent. The stereochemical assignment for the generated cyclopropanes was achieved by X-ray crystallography or comparing with the reported spectroscopic data. We found that the diastereoselectivity was influenced by several factors, including the protecting groups, solvents, and temperatures, and good anti/syn ratios (>10:1) were often obtained using the tert-butyldimethylsilyl and tert-butyldiphenylsilyl-protected substrates. The method was applied to a formal synthesis of a natural eicosanoid with good efficiency.
