Total synthesis of indole-derived allocolchicine analogues exhibiting strong apoptosis-inducing activity.

A series of novel pyrrolo-allocolchicine derivatives (containing a 1-methyl-1H-indol-5-yl moiety replacing ring C) was synthesized. The tetracyclic ring system was constructed by Suzuki-Miyaura cross-coupling of a 1-methylindole-5-boronate with an ortho-iodo-dihydrocinnamic acid derivative and subsequent intramolecular Friedel-Crafts acylation. After reduction of the resulting ketone, the nitrogen functionality was introduced in a Mitsunobu-type reaction by using zinc azide followed by LiAlH(4) reduction.

Paraoxonase-1 is a major determinant of clopidogrel efficacy.

Clinical efficacy of the antiplatelet drug clopidogrel is hampered by its variable biotransformation into the active metabolite. The variability in the clinical response to clopidogrel treatment has been attributed to genetic factors, but the specific genes and mechanisms underlying clopidogrel bioactivation remain unclear. Using in vitro metabolomic profiling techniques, we identified paraoxonase-1 (PON1) as the crucial enzyme for clopidogrel bioactivation, with its common Q192R polymorphism determining the rate of active metabolite formation.

Anti-inflammatory arene--chromium complexes acting as specific inhibitors of NOD2 signalling.

Inflammation is a hallmark of microbial infection in mammals and is the result of a pathogen-induced release of inflammatory effectors. In humans a variety of germ-line encoded receptors, so-called pattern-recognition receptors, respond to conserved signatures on invading pathogens, which results in the transcriptional activation of pro-inflammatory responses. Inflammation is often detrimental to the host and leads to tissue damage and/or systemic dysfunctions.

trans-Ethyl-enedi-p-phenyl-ene diacetate.

The centrosymmetric title compound, C(18)H(26)O(4), was prepared in high yield from 4-acetoxy-styrene via Ru-catalysed homo-olefin metathesis. Exclusive formation of the E-configurated isomer was observed. In the crystal, a strong C-H⋯π inter-molecular inter-action links the mol-ecules together.

trans-1,2-Bis(3,5-dimethoxy-phen-yl)ethene.

The title compound, C(18)H(20)O(4), was prepared in high yield from 3,5-dimethoxy-styrene via a Ru-catalysed homo-olefin metathesis. Exclusive formation of the E-configurated isomer was observed. Inter-estingly, one symmetric unit contains two mol-ecules adopting an s-syn-anti and and an all-s-anti conformation.

Studies toward the total synthesis of mumbaistatin, a highly potent glucose-6-phosphate translocase inhibitor. Synthesis of a mumbaistatin analogue.

A strategy for the total synthesis of the highly potent glucose-6-phosphate translocase inhibitor mumbaistatin (1) and structural analogues was elaborated. Such compounds represent a lead structure in the development of potential new drugs for the treatment of diabetes. To evaluate the general strategy, the close mumbaistatin analogue 10 was synthesized in a convergent manner.