The development of novel organic reactions and their applications in the synthesis of complex molecules of biological and pharmaceutical importance.
Organic synthesis continues to be a fundamentally significant area of scientific research. In fact, the discovery of many important and useful reactions and synthetic strategies in the past several decades has enabled a plethora of downstream scientific endeavors, ranging from drug discovery and chemical biology to surface chemistry and soft materials. The research focus in the Kartika group has been mainly directed towards the development of new synthetic chemistries that are inspired by natural products. Natural products are privileged chemical entities known as secondary metabolites. The vast structural complexity inherent to this class of molecules often enables them to exhibit specific biological functions, thus making natural products highly relevant in modern drug discovery. In fact, over 50% of all newly approved small-molecule chemical entities ranging from antibacterial to anticancer drugs in the past 30 years have been derived from natural products.
Research in natural product chemistry is an essential component of the Kartika group. We primarily focus on organic syntheses, particularly in the development of novel synthetic methodology and application in total synthesis of natural products. Examples of the ongoing research programs in the Kartika group include:
Chlorosulfolipid Natural Products
Chlorosulfolipids are a class of natural products that are essentially assembled by a long hydrocarbon chain with multiple chlorine, sulfate, and/or hydroxy substitutions along their aliphatic backbone. The intricate structural features in these molecules represent profound synthetic challenges, especially concerning the lack of stereoselective reactions involving complex polychlorinated hydrocarbons. Our group recently developed a new strategy to introduce carbon-chlorine bonds from unreactive aliphatic alcohols via activation with triphosgene and pyridine under mild conditions. This chemistry was found to be highly stereosepecific and could be readily extended towards the one-pot conversion of aliphatic polyols to the corresponding alkyl polychlorides in a highly diastereoselective manner. We also discovered that application of this triphosgene-pyridine activation towards ketones readily produced vinyl chlorides, a common functionality in chlorosulfolipids.
New Reactions with Oxyallyl Cations
Inspired by the structural features in hapalindole alkaloid natural products and the synthetic challenges associated with an incorporation of substituted indoles at the a-position of carbonyl compounds, we recently developed a series of reactions by exploiting the utility of unsymmetrical oxyallyl cations that are generated under mild Brønsted acid catalysis as the key intermediates. Our investigation revealed that by simply protecting these reactive species at the oxygen center, the ensuing nucleophilic addition could be readily directed towards a specific electrophilic carbon in a highly regioselective manner. Overall, these new chemistries have been found to be extremely robust and tolerated by a broad scope of substrates and nucleophiles, thus enabling the construction of various synthetically important molecular scaffolds and pharmaceutically relevant heterocyclic compounds.