Recent methods for diversification of bile acids and related steroids towards supramolecular.

Bile acids (BAs) are a class of steroidal surfactants that have been studied as building blocks for constructing useful chemical frameworks. These starting materials have rigid structures with defined hydrophobic and hydrophilic faces, which promotes self-assembly in well-defined chemical architectures. The BA scaffolds can undergo a variety of transformations to introduce a range functionalities with practical applications. These functionalized derivatives have seen application in pharmacology, supramolecular chemistry, and nanotechnology in roles such as surfactants, gelators, drug conjugates, or chemical detectors. This review seeks to highlight recent synthetic methods utilizing BAs to construct useful chemical structures and their application in supramolecular chemistry.

Multicapillary Flow Reactor: Synthesis of 1,2,5-Thiadiazepane 1,1-Dioxide Library Utilizing One-Pot Elimination and Inter-/Intramolecular Double aza-Michael Addition Via Microwave-Assisted, Continuous-Flow Organic Synthesis (MACOS).

A microwave-assisted, continuous-flow organic synthesis (MACOS) protocol for the synthesis of functionalized 1,2,5-thiadiazepane 1,1-dioxide library, utilizing a one-pot elimination and inter-/intramolecular double aza-Michael addition strategy is reported. The optimized protocol in MACOS was utilized for scale-out and further extended for library production using a multicapillary flow reactor. A 50-member library of 1,2,5-thiadiazepane 1,1-dioxides was prepared on a 100- to 300-mg scale with overall yields between 50 and 80% and over 90 % purity determined by proton nuclear magnetic resonance (1H-NMR) spectroscopy.

Application of a Double Aza-Michael Reaction in a 'Click, Click, Cy-Click' Strategy: From Bench to Flow.

The development of a 'click, click, cy-click' process utilizing a double aza-Michael reaction to generate functionalized 1,2,5-thiadiazepane 1,1-dioxides is reported. Optimization in flow, followed by scale out of the inter-/intramolecular double aza-Michael addition has also been realized using a microwave-assisted, continuous flow organic synthesis platform (MACOS). In addition, a facile one-pot, sequential strategy employing in situ Huisgen cycloaddition post-double aza-Michael has been accomplished, and is applicable to library synthesis.