Lucia Garcia de la Parte

Trimethylsilyl ethers of monoprotected isosorbide derivatives have been subjected to multicomponent Hosomi–Sakurai reactions with allyl trimethylsilane and various aldehydes (aromatic or aliphatic) under the catalysis of trimethylsilyl triflate. This study has allowed for establishing that: (a) the best results are obtained in reactions involving TMS ethers of the endo-OH group; (b) the most suited protecting group is the tert-butyldiphenylsilyl ether. With this ideal substrate, a scope was studied using both aromatic and aliphatic aldehydes. Good yields and excellent diastereoselectivities were typically achieved with aromatic aldehydes, unless they were very encumbered at the ortho position or strongly electron-poor. With simple aliphatic enolizable aldehydes, it may be useful to use an excess of aldehydes because of self-condensation processes. These results open the way to conjugates of bio-based isosorbide with aldehyde-derived fragments, joined through a very stable ether group.

A general Prins-type cyclization with ketone substrates that enables the efficient and stereoselective construction of tetrahydropyrans bearing quaternary carbon centers is described.

Transition metal catalysis has contributed to the discovery of novel methodologies and the preparation of natural products, as well as new chances to increase the chemical space in drug discovery programs. In the case of marine drugs, this strategy has been used to achieve selective, sustainable and efficient transformations, which cannot be obtained otherwise. In this perspective, we aim to showcase how a variety of transition metals have provided fruitful couplings in a wide variety of marine drug-like scaffolds over the past few years, by accelerating the production of these valuable molecules.

In this perspective, we showcase the benefits of continuous flow chemistry and photochemistry and how these valuable tools have contributed to the synthesis of organic scaffolds from the marine environment. These technologies have not only facilitated previously described synthetic pathways, but also opened new opportunities in the preparation of novel organic molecules with remarkable pharmacological properties which can be used in drug discovery programs.