Fanny Chui-Fun Ip

Highly trans-Selective Arylation of Achmatowicz Rearrangement Products by Reductive γ-Deoxygenation and Heck–Matsuda Reaction: Asymmetric Total Synthesis of (−)-Musellarins A–C and Their Analogues

Fully functionalized pyranuloses derived from Achmatowicz rearrangement (AR) are versatile building blocks in organic synthesis. However, access to trans-2,6-dihydropyrans from pyranuloses remains underexplored. Herein, we report a new two-step trans arylation of AR products to access 2,6-trans-dihydropyranones. This new trans-arylation method built on numerous plausible, but unsuccessful, direct arylation reactions, including Ferrier-type and Tsuji-Trost-type reactions, was finally enabled by an unprecedented, highly regioselective γ-deoxygenation of AR products by using Zn/HOAc and a diastereoselective Heck-Matsuda coupling. The synthetic utility of the reaction was demonstrated in the first asymmetric total synthesis of (-)-musellarins A-C and 12 analogues in 11-12 steps. The brevity and efficiency of our synthetic route permitted preparation of enantiomerically pure musellarins and analogues (>20 mg) for preliminary cytotoxicity evaluation, which led us to identify two analogues with three-to-six times greater potency than the musellarins as promising new leads.

Recent Development in the Search for Effective Antidepressants Using Traditional Chinese Medicine

Depressive disorder is a common illness that affects millions of people worldwide and the patients often suffer from symptoms such as depressed mood, sleep disturbances, and suicidal ideation. Since the approval of fluoxetine in the United States nearly 20 years ago, the annual prescription of antidepressants has increased rapidly. However, despite the increasing number of new antidepressants introduced to the clinic, the quality of treatment still remains poor due to the delayed response or low efficacy often associated with these synthetic antidepressants. Thus, there have been a growing number of patients turning to alternative medicine treatments for a more effective cure. To date, one of the most frequently used and well-studied herbal preparation for mild and moderate depression is the extract of St Johns wort. However, recent report has indicated that drug interaction of this herb with other antidepressants may result in severe clinical consequences. Traditional Chinese medicine (TCM) has a long history of use in China with a proven record of high efficacy and low toxicity. It is also an excellent source of diverse and complex chemicals that possess a wide variety of biological activities. In recent years, TCM has received growing attention as an alternative or adjuvant therapy to Western medicine treatments and a large volume of efforts have been directed towards the identification of potential antidepressive phytomedicine from TCM. Potential TCM-derived therapeutics including herbal formulations, extracts, and individual active constituents have been evaluated with behavioral animal models and clinical studies. This article will review the recent development in the search for effective antidepressive therapeutics using TCM. Literatures published in Chinese will also be reviewed to include the recent advances in this area. Moreover, our group has been using a knowledge-based approach to identify active ingredients for the treatment of neurological disorders. The workflow of our approach will also be discussed.