Dr. Zhong-Yan Cao

Prof. Paolo Melchiorre

Driving asymmetric photoreactions by merging organo- and gold-catalysis

From 06/05/2016 to

05/05/2018

PHOTO-ORGANO-GOLD

We are in a changing era for drug discovery: the growing perception is that basic chemical research will play a greater role in
pharmaceutical development. One current challenge is to develop a new kind of chemistry that yields a screening collection
comprising optimal chiral molecules that increase the probability of success in identifying drug-candidate structures. Also,
the chemistry community has recently recognized how visible light-mediated photoreactions can open new avenues in
modern organic synthesis and the past seven years have witnessed its remarkable prosperity. Therefore, developing photofacilitated
asymmetric reactions focusing on rapidly generating privileged chiral natural-like compounds for drug discovery
are highly desirable.
The proposed research aims to combine the fellow’s experience in gold catalysis and the host’s experience in phototriggered
organocatalysis (two powerful fields of molecule activation, which have to date remained unrelated) to develop
otherwise unachievable catalytic asymmetric photoreactions. Specifically, we will focus on using readily available,
unactivated aryl/alkyl chloride or bromide, which cannot be easily activated by the commonly used Rh- or Ir-based
photoredox catalysts. The resulting strategies will be used as an ideal platform for assembling libraries comprising
enantiopure chiral small molecules bearing α,α-disubstituted α-amino acid & 3,3-disubstituted oxindole frameworks, which,
along with biological screening carried out in collaboration with a world-wide recognized pharma-company (Lundbeck A/S,
Copenhagen, DK), will increase the probability of success in identifying drug-candidate structures.

Enantioselective radical conjugate additions driven by a photoactive intramolecular iminium-ion-based EDA complex
Z. Cao, T. Ghosh, P. Melchiorre
Nat. Commun. 2018, 9 (3274)
DOI: 10.1038/s41467-018-05375-2

ICIQ School

27-29th September 2017; Tarragona (Spain)