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Biomedical subjects

Emmanuel A Theodorakis

Publications and source records attributed to Emmanuel A Theodorakis.

28 records · Page 2Linked to original sources
PubMed2003

Novel synthesis of 2'-O-methylguanosine.

An efficient and chemoselective synthesis of 2'-O-methylguanosine (6) has been accomplished in high yield without protection of the guanine base. The salient feature of the synthesis of 6 lies in the application of methylene-bis-(diisopropylsilyl chloride), (MDPSCl(2), 2) as a new 3',5'-O-protecting group for nucleosides. Use of CH(3)Cl as a weak electrophile and NaHMDS as a mild base was crucial to the success of the 2'-O-methylation of 3',5'-O-protected guanosine.

Guanosine↗
PubMed2003

Regioselective synthesis of the tricyclic core of lateriflorone.

An efficient synthetic approach to the tricyclic core 8 of lateriflorone is described. Essential to the synthesis was the implementation of a biomimetic tandem Claisen/Diels-Alder reaction that produced the desired tricyclic scaffold as a single isomer. A rationalization of the excellent regio and stereoselectivity of this transformation is also proposed. [reaction: see text]

Cyclization↗
PubMed2003

Anti-TNF-alpha therapies: the next generation.

The functioning of the immune system is finely balanced by the activities of pro-inflammatory and anti-inflammatory mediators or cytokines. Unregulated activities of these mediators can lead to the development of serious inflammatory diseases. In particular, enhanced tumour-necrosis factor-alpha (TNF-alpha) synthesis is associated with the development of rheumatoid arthritis, psoriatic arthritis and inflammatory bowel disease. Inhibiting TNF-alpha activities in these diseases has been remarkably successful. However, the current injectable protein therapies have associated risks and limitations. An oral, small molecule that regulates TNF-alpha biology could either replace the injectables or provide better disease control when used alone or in conjunction with existing therapies. In this review, we discuss briefly the present understanding of TNF-alpha-mediated biology and the current injectable therapies in clinical use, and focus on some of the new therapeutic approaches with oral, small-molecule inhibitors.

Animals↗
PubMed2002

Synthesis of 2'-O-methoxyethylguanosine using a novel silicon-based protecting group.

A short and efficient synthesis of 2'-O-methoxyethylguanosine (8) is described. Central to this strategy is the development of a novel silicon-based protecting group (MDPSCl(2), 2) used to protect the 3',5'-hydroxyl groups of the ribose. Silylation of guanosine with 2 proceeded with excellent regioselectivity and in 79% yield. Alkylation of the 2'-hydroxyl group of 6 proceeded with methoxyethyl bromide and NaHMDS and afforded compound 7 in 85% yield, without any noticeable cleavage of the silyl protecting group and without the need to protect the guanine base moiety. Finally, deprotection of 7 was achieved using TBAF and produced 8 in 97% yield.

Alkylation↗
PubMed2002

Unified synthesis of quinone sesquiterpenes based on a radical decarboxylation and quinone addition reaction.

A unified synthesis of several quinone sesquiterpenes is described herein. Essential to this strategy is a novel radical addition reaction that permits the attachment of a fully substituted bicyclic core 16 to a variably substituted quinone 10. The addition product 15 can be further functionalized, giving access to natural products with a high degree of oxygenation at the quinone unit. The quinone addition reaction is characterized by excellent chemoselectivity, taking place only at conjugated and unsubstituted double bonds, and regioselectivity, being strongly influenced by the resonance effect of heteroatoms located on the quinone ring. These features were successfully applied to the synthesis of avarol (1), avarone (2), methoxyavarones (4, 5), ilimaquinone (6), and smenospongidine (7), thereby demonstating the synthetic value of this new method.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Regioselective synthesis of the bridged tricyclic core of Garcinia natural products via intramolecular aryl acrylate cycloadditions.

[reaction: see text] Two different routes to the tricyclic core of Garcinia-derived natural products are described. The first approach is based on a tandem Claisen/Diels-Alder rearrangement and delivers the desired lactone 14. The second approach, employing a Wessely oxidation/Diels-Alder protocol, leads to the same caged heterocycle, albeit with modified constitution.

Acrylates↗
PubMed2002

Synthesis of (-)-ilimaquinone via a radical decarboxylation and quinone addition reaction.

[reaction: see text] A stereoselective synthesis of (-)-ilimaquinone (4) is presented. The synthetic strategy is based on a novel radical decarboxylation and quinone addition methodology that produces quinone 7 from reaction of thiohydroxamic acid derivative 8 with benzoquinone (9). Final functionalization of 7 to ilimaquinone (4) is achieved by exploring the electronic effects of the residual thiopyridyl group.

Animals↗
PubMed2002

Phospholipid-bound molecular rotors: synthesis and characterization.

Molecular rotors are fluorescent molecules with a viscosity-sensitive quantum yield that are often used to measure viscosity changes in cell membranes and liposomes. However, commercially available molecular rotors, such as DCVJ (1) do not localize in cell membranes but rapidly migrate into the cytoplasm leading to unreliable measurements of cell membrane viscosity. To overcome this problem, we synthesized molecular rotors covalently attached to a phospholipid scaffold. Attaching the rotor group to the hydrophobic end of phosphatidylcholine (PC) did not affect the rotor's viscosity sensitivity and allowed adequate integration into artificial bilayers as well as complete localization in the plasma membrane of an endothelial cell line. Moreover, these new rotors enabled the monitoring of phospholipid transition temperature. However, attachment of the rotor groups to the hydrophilic head of the phospholipid led to a partial loss of viscosity sensitivity. The improved sensitivity and exclusive localization in the cell plasma membrane exhibited by the phospholipid-bound molecular rotors suggest that these probes can be used for the study of membrane microviscosity.

Cell Line↗
PubMedDate not supplied

MDPSCL2: a new protecting group for chemoselective synthesis of 2'-O-alkylated guanosines.

An improved strategy for the synthesis of 2'-O-methyl-guanosine (6) and 2'-MOE-guanosine (8) is reported. The regioselectivity of the alkylation was attained using a novel silicon-based protecting group, methylene-bis (diisopropyl-silylchloride) (MDPSCl2, 2). The alkylation proceeded in a chemoselective manner using NaHMDS as the base and MeCl or MOE-Br as the appropriate electrophiles.

Alkylation↗