No Added Chemicals

One of the main attractions in the chemistry of natural products, apart from facing new challenges in synthetic methodologies, is discovering a novel therapeutic agent such as ecteinascidin 743 (ET-743) . This compound was isolated for the first time as pure compound from Caribbean tunicate Ecteinascidia turbinata in 1986 by Rinehart's group. This compound possess interesting properties as a potent anti-tumour agent and ET-743 is approved in Europe, Russia and South Korea for treatment of advanced soft tissue sarcoma. From synthetic chemists' point of view, ET-743 provides an interesting challenge as it has interesting molecular architecture; comprised of eight rings, including 10-membered heterocycles and 8 stereogenic centres. This interesting molecular architecture and interesting anti-tumour properties were the motivation of its first total synthesis by E. J. Corey in 1996.

Previously, in asymmetric aldol reaction a chiral enolate is used to ensure diastereoselective reaction by introducing more control due to chiral centre at enolate or carbonyl. This time, another method is used to synthesis an enantiopure product which is using chiral auxiliary functional group. Chiral auxiliary-controlled aldol reaction In this method, an enantiopure auxiliary (X C ) is used and it carries out a diastereoselective reaction such as aldol reaction. Furthermore, the reaction provides enantiopure product after removal of the chiral auxiliary.

One of the well-known reactions in C-C bond formation is aldol reaction. This robust reaction has a great potential in controlling two stereocentres of the product. General aldol reaction The control on the stereocentres of the product is determined from the stereochemistry of the formed enolate; Z - and E - enolates would give different control on the outcome of aldol products.

In nucleophilic addition in carbonyl compounds, it involves breaking π(C=O) bond by adding electrons into C=O antibonding orbitals. This implies the trajectory of attack for addition of a nucleophile follows the shape  of π*(C=O) allowing proper overlap with the orbitals. The trajectory of this nucleophile is around 107-109° and this angle is called Bürgi-Dunitz angle; named after H. B. Bürgi and J. D. Dunitz who discovered the physical evidence that supports the this angle of attack (H. B. Bürgi, J. D. Dunitz, and E. Shefter, J. Am. Chem. Soc., 1973, 95 , 5065-5067). Bürgi-Dunitz angle and the evidence of the trajectory of nucleophilic attack.