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Follicle-stimulating hormone (FSH), acting on its receptor (FSHR), plays a pivotal role in the stimulation of follicular development and maturation. Multiple injections of protein formulations are used during clinical protocols for ovulation induction and for in vitro fertilization that are followed by a selection of assisted reproductive technologies. In order to increase patient convenience and compliance several research groups have searched for orally bioavailable FSH mimetics for innovative fertility medicines. We report here the discovery of a series of substituted benzamides as positive allosteric modulators (PAM) targeting FSHR. Optimization of this series has led to enhanced activity in primary rat granulosa cells, as well as remarkable selectivity against the closely related luteinizing hormone receptor (LHR) and thyroid stimulating hormone receptor (TSHR). Two modulators, 9j and 9k, showed promising in vitro and pharmacokinetic profiles.

ABC and EF ring fragments of spirolucidine have been prepared via asymmetric synthesis using chiral N-acylpyridinium salt chemistry. Model studies have been carried out to support further progress toward the completion of this complex alkaloid.

Dendrimers can be obtained in precise molecular weights even at high generations. This feature, as well as the inherent globular shape of high generation dendrimers, makes them ideal candidates for macromolecular biomimetics. In this account, we discuss the synthesis and use of dendrimers that are reminiscent of macromolecular architectures present in nature. In particular, we focus the use of dendrimers in the areas of encapsulation, functionalization, and sequencing. To cite this article: S. Thayumanavan et al., C. R. Chimie 6 (2003).

Aromatic aldehydes and imines are converted to the corresponding diols and diamines using the low valent titanium species generated by the reaction of TiCl 4 with triethylamine.

Polycyclic aromatic hydrocarbon radical anions, prepared by the addition of sodium to the aromatic hydrocarbon in THF, undergo acylation with carboxylic acid esters and formylation with N N-dialkylformamides.

Alkynyltitanium species, prepared in situ from alk-1-ynes using the TiCl4/Et3N reagent system, react with aromatic aldehydes to give enynones 2 in 49–38% yields. Reaction of alkynyl aryl ketones with aromatic aldehydes and the TiCl4/Et3N reagent gives the enynones 2 in 78–92% yields.

Polycyclic aromatic hydrocarbon radical anions, prepared by the addition of sodium to the aromatic hydrocarbon in THF, undergo acylation with carboxylic acid esters and formylation with N N-dialkylformamides.

Aromatic aldehydes and imines are converted to the corresponding diols and diamines using the low valent titanium species generated by the reaction of TiCl 4 with triethylamine.

Iminium salts are generated in situ, react with TiCl4-trialkylamines, and diaryl ketones to produce 3,3-diaryl-cyclobutanones in moderate to good yields.

Alkynyltitanium reagents are prepared in situ in the reaction of 1-alkynes with TiCl4/Et3N and are used in the reaction with certain electrophiles.

TiCl4 reacts with trialkylamines at 0−25 °C to give iminium ions that on metalation followed by reaction with diaryl ketones, produce α,β-unsaturated aldehydes.

A new route to C2-symmetric diamines via an asymmetric reductive dimerization of 1-acylpyridinium salts and their benzo derivatives is described. This method is practical as the starting heterocycles and chiral auxiliaries are readily available. The titanium reducing agent is inexpensive and easy to prepare. Several novel enantiopure C2-symmetric diamine derivatives were synthesized using this method.

Alkynyltitanium species, prepared in situ from alk-1-ynes using the TiCl 4 /Et 3 N reagent system, react with aromatic aldehydes to give enynones 2 in 49-38% yields. Reaction of alkynyl aryl ketones with aromatic aldehydes and the TiCl 4 /Et 3 N reagent gives the enynones 2 in 78-92% yields.

[reaction: see text] The iminium ions generated in situ by the oxidation of N,N-diisopropyl-N-benzylamine using iodine react with diaryl ketones in the presence of TiCl4/R3N to give the corresponding 3,3-diarylcyclobutanones in moderate to good yields (49-86%). The 3,3-diarylcyclobutanone iminium ions formed in this transformation was reduced in situ with B2H6 to produce the corresponding 3,3-diarylcyclobutylamines (52-79% yields), a class of compounds with potential antidepressant activity. In addition, a series of N,N-dimethyl-3,3-diarylcyclobutylamines were synthesized by the reductive amination of the corresponding 3,3-diarylcyclobutanone derivatives.

[reaction: see text] Design and synthesis of a novel class of dendrons based on an AB(4) monomer are described. These dendrons have been evaluated by using dendritic encapsulation of a redox active core. The electrochemical properties of symmetric ferrocene-cored dendrimers show that significant alterations in redox potential and heterogeneous electron-transfer rate constants could be achieved even at lower generations.

Iminium salts are generated in situ, react with TiCl4-trialkylamines, and diaryl ketones to produce 3,3-diaryl-cyclobutanones in moderate to good yields.

[see reaction]. Design and synthesis of a novel class of monodendrons, in which the functional units can potentially be directed toward the concave interiors of dendrimers, are described. The key feature of the design is the placement of the amphiphilic and the AB2 functional groups in orthogonal planes.