A series of eight novel bis(oxazoline) ligands incorporating gem-disubstitution on one of the oxazoline rings were prepared from (S)-valine. These ligands are designed as a cost-effective alternative to similar ligands possessing an oxazolinyl C(5)-tert-butyl group derived from expensive (S)-tert-leucine. Four of the ligands possess a C(4)-gem-dimethyl group and four a C(4)-gem-diphenyl group adjacent to the C(5)-isopropyl substituent. Zinc complexes of ligands 11a-h, along with non-C(4)-gem-disubstituted analogues 1a-g, were effective in the Friedel-Crafts alkylation of both indole (up to 74% ee) and 2-methoxyfuran (up to 95% ee) with a series of nitroalkenes. Three of the ligands (11a-c), an iron dichloride complex of ligand 11d and two zinc dichloride complexes, were characterized by X-ray crystallography, one with ligand 11d and the second a bis-tert-butyl-substituted N-methylamine ligand. A direct comparison of the latter structures clearly illustrates the gem-dimethyl effect.

Bis(oxazolines) are a well-known class of ligands in the area of asymmetric catalysis. Most of these ligands are C 2 -symmetric due to the synthetic route employed for their synthesis. This review article summarizes the recent progress of the closely related, but relatively unexplored, C 1 -symmetric bis(oxazoline) ligands and compares and contrasts the two where applicable.

Systemic sclerosis (SSc) is an autoimmune connective tissue disease in which there is elevated inflammation, aberrant cytokine expression, and subsequent fibrosis. Interleukin‐11 (IL‐11) is a recently described profibrotic cytokine that can mediate fibrosis in the heart, lungs, and skin and is upregulated by transforming Growth Factor‐β (TGF‐β1). The objective of this study was to quantify the serum levels of IL‐11 in early diffuse SSc patients. Also, if IL‐11 could regulate the alarmin IL‐33 in dermal fibroblasts was quantified. Early diffuse SSc patient sera was isolated and IL‐11 was quantified by specific commercial ELISA compared to healthy control (n = 17). Healthy dermal fibroblasts were cultured in vitro and then serum starved and incubated with or without recombinant IL‐11. At specific early and late time points the supernatant was quantified for the alarmin IL‐33 by specific ELISA. In early diffuse SSc patients it was demonstrated that they have elevated IL‐11 in their sera. In a subgroup of SSc patients with interstitial lung disease (ILD) this elevation was particularly pronounced compared to those devoid of fibrotic lung disease. In vitro incubation of healthy dermal fibroblasts led to a significant induction of IL‐33 cytokine release into the cell media. IL‐11 is a profibrotic cytokine that is elevated in early diffuse SSc and is particularly elevated in those with ILD. This suggests that IL‐11 could be a possible biomarker of ILD in SSc. It was also found that IL‐11 led to release of the cytokine alarmin IL‐33 in fibroblasts at earlier time points but not late time points, suggesting early stimulation elicits an inflammatory response in the local microenvironment but prolonged stimulation leads to fibrosis.

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