Periodic Reporting for period 1 - silvercatpharma (from gold to silver: streamlining metal-catalysed cross-coupling reactions)
Okres sprawozdawczy: 2015-04-01 do 2017-03-31
The development of reactions within the context of SILVERCATPHARMA represents the basis for the synthesis of bioactive molecules in Novartis; in the future these compounds can be potential candidates for the treatment of important diseases and so be the foundation for treatments that will reach thousands of people. In so doing we desire to show how basic research, such as the use of d-11 blocks metals in synthesis, plays a pivotal role for the disclosure of new molecules that can have a future effect on the population.
SILVERCATPHARMA takes into account the important of the formation of new carbon-carbon bonds at an industrial level. For this reason it aims at the design of new metal-catalysed C-C reactions under mild conditions through the exploitation of small nanoclusters. The use of gold in this sense will help in to understand of the basic reactivity principles. Then, the attention will move onto gol-silver clusters as potential catalysts for the above mentioned reactions. Gold nanoclusters are a promising class of model catalysts. They will provide new opportunities for the comprehension of metal nanocatalysis and for the new design of highly selective catalysts for specific chemical processes. The possibility of a rational design of gold and silver clusters for the synthesis of fine chemicals represents a way to optimize the outcome of reactions.
In conclusion, we were still able to promote a [2+2] cycloaddition reaction promoted by gold and we demonstrated its usefulness in the total synthesis of two natural compounds, rumphellanone and hushinone. These results were made visible by:
High impact publications (the last one just submitted).
- Synthesis of Rumphellaone A and Hushinone by a Gold-Catalyzed [2+2] Cycloaddition
Org. Lett. 2016, 18, 1614-1617.
- Enantioselective Synthesis of Cyclobutenes by Intermolecular [2+2] Cycloaddition with Non-C2 Symmetric Digold Catalysts (submitted)
A review article was also published:
- Anatomy of gold catalysts: facts and myths
Org. Biomol. Chem. 2015, 13, 7103-7118.
Oral and written presentation in international congresses:
1. OMCOS, June 28th- July 2nd 2015, Sitges- Barcelona, Spain (poster).
2. 24th International Symposium: Synthesis in Organic Chemistry, July 20th-23rd 2015, Cambridge, UK (poster).
3. IKCOC-13, November 9th-13th 2015, Kyoto, Japan (oral presentation).
4. Gordon Research Conference on Natural Products & Bioactive Compounds, July 31st-August 5th 2016, Proctor Academy in Andover (NH), United States (poster).
The interest on this catalysis does not belong only to academic settings but industrial as well, as witnessed by the work carried out in Novartis (ongoing projects, still not completed): two molecules have been synthesised and they are currently subjected to in vivo and in vitro studies. Moreover, this industrial interest can result in the application of the chemistry for the synthesis of biologically active compounds. This industrial interest and application is still at is infancy and beneficial and broad effects will be seen in the due course."