Application of environmental-friendly reactions in high-value compound synthesis : synthetic studies towards the total synthesis of dactylolide

• Main Author: Wong, Zhen Zhou
• Other Authors: Liu Chuan Fa
• Format: Theses and Dissertations
• Language: English
• Published: 2017
• Subjects: DRNTU::Science::Chemistry::Organic chemistry::Organic synthesis
• Online Access: http://hdl.handle.net/10356/70603
• Institution: Nanyang Technological University

This work aimed to demonstrate the feasibility of two environmental-friendly reactions that developed in Loh’s research group in the racemic synthesis of dactylolide (2), a marine natural product which is a potential candidate for anti-cancer treatment. Syntheses of two major components of dactylolide, namely C1-C8 fragment (C3-2) and C9-C19 fragment (AB-1b-I) were achieved in this study with two key strategies, which were In(OTf)3-catalyzed intramolecular 2,5-oxonium-ene cyclization and Pd-catalyzed direct cross-coupling reaction. Both strategies provided access to southern 2,6-syn-4-exomethylene tetrahydropyran motif and northern conjugated dienoate structure respectively. C9-C19 fragment (AB-1b-I) was convergently synthesized from two parallel syntheses, which provided conjugated aldehyde A2 and homoallylic alcohol B2-2 as precursor for tetrahydropyran synthesis. On the other hand, synthesis of C1-C8 fragment (C3-2) was achieved with a 5-step transformation from epichlorohydrin. This established route utilized convergent strategy, catalytic bond-forming reactions and employed less hazardous chemicals, which showed greener access to target fragments.