“…In this review, we have introduced neurotrophin-mimicking natural products discovered by our group and have focused on the chemical and biological features of neurotrophic compounds but have not emphasized their synthetic achievements, because there are already some excellent reviews on this subject [ 18 , 104 , 150 ] that summarize the overview of their organic syntheses. Endogenous neurotrophins (NGF, BDNF etc.)…”
Section: Discussionmentioning
confidence: 99%
“…Then, epoxidation of 43 with m -chloroperoxybenzoic acid ( m -CPBA) proceeded in a highly stereoselective fashion to give 44 , which was treated with p -toluenesulfonic acid ( p -TsOH) to produce merrilactone A ( 37 ) in 78% yield (Scheme 6 ). Following our reports, a number of excellent total syntheses of merrilactone A were published, and one should take a look at references [ 103 , 104 ] for the details of each synthesis. Scheme 6 Partial synthesis of 37 from anislactone B ( 42 ) …”
Section: Neurotrophic Compounds From
Illicium
Specmentioning
Neurotrophic factors, now termed neurotrophins, which belong to a class of polypeptidyl agents, have been shown to potentially be beneficial for the treatment of neurodegenerative diseases such as Alzheimer's disease, because endogenous neurotrophic factors (NGF, BDNF, NT3, NT4) have been recognized to play critical roles in the promotion of neurogenesis, differentiation, and neuroprotection throughout the development of the central nervous system. However, high-molecular weight proteins are unable to cross the blood-brain barrier and are easily decomposed by peptidase under physiological conditions. To address this issue, small molecules that can mimic the functions of neurotrophic factors would be promising alternatives for the treatment of neurodegenerative disease. We have continued to search for natural products having typical neurotrophic properties, which can cause neurogenesis, enhance neurite outgrowth, and protect neuronal death using three cellular systems (PC12, rat cortical neurons, and MEB5 cells). In this review, we summarize the neurotrophic activities and synthesis of dimeric isocuparane-type sesquiterpenes from the liverwort, Mastigophora diclados, the mechanism of neurotrophic neolignans, magnolol, honokiol and their sesquiterpene derivatives, and introduce unique neurotrophin-mimic natural products, including seco-prezizaane-type sesquiterpenes from the Illicium species, vibsane-type diterpenes from Viburnum awabuki, and miscellaneous natural products with neurotrophic effects discovered by us.
“…In this review, we have introduced neurotrophin-mimicking natural products discovered by our group and have focused on the chemical and biological features of neurotrophic compounds but have not emphasized their synthetic achievements, because there are already some excellent reviews on this subject [ 18 , 104 , 150 ] that summarize the overview of their organic syntheses. Endogenous neurotrophins (NGF, BDNF etc.)…”
Section: Discussionmentioning
confidence: 99%
“…Then, epoxidation of 43 with m -chloroperoxybenzoic acid ( m -CPBA) proceeded in a highly stereoselective fashion to give 44 , which was treated with p -toluenesulfonic acid ( p -TsOH) to produce merrilactone A ( 37 ) in 78% yield (Scheme 6 ). Following our reports, a number of excellent total syntheses of merrilactone A were published, and one should take a look at references [ 103 , 104 ] for the details of each synthesis. Scheme 6 Partial synthesis of 37 from anislactone B ( 42 ) …”
Section: Neurotrophic Compounds From
Illicium
Specmentioning
Neurotrophic factors, now termed neurotrophins, which belong to a class of polypeptidyl agents, have been shown to potentially be beneficial for the treatment of neurodegenerative diseases such as Alzheimer's disease, because endogenous neurotrophic factors (NGF, BDNF, NT3, NT4) have been recognized to play critical roles in the promotion of neurogenesis, differentiation, and neuroprotection throughout the development of the central nervous system. However, high-molecular weight proteins are unable to cross the blood-brain barrier and are easily decomposed by peptidase under physiological conditions. To address this issue, small molecules that can mimic the functions of neurotrophic factors would be promising alternatives for the treatment of neurodegenerative disease. We have continued to search for natural products having typical neurotrophic properties, which can cause neurogenesis, enhance neurite outgrowth, and protect neuronal death using three cellular systems (PC12, rat cortical neurons, and MEB5 cells). In this review, we summarize the neurotrophic activities and synthesis of dimeric isocuparane-type sesquiterpenes from the liverwort, Mastigophora diclados, the mechanism of neurotrophic neolignans, magnolol, honokiol and their sesquiterpene derivatives, and introduce unique neurotrophin-mimic natural products, including seco-prezizaane-type sesquiterpenes from the Illicium species, vibsane-type diterpenes from Viburnum awabuki, and miscellaneous natural products with neurotrophic effects discovered by us.
“…Against this backdrop of structural intricacies and fascinating biological activities, over 30 inspired syntheses of these molecules have been disclosed . Multiple groups, spanning decades of synthetic investigations, have reported total and formal syntheses of jiadifenolide ( 2 ), jiadifenin ( 3 ), 11- O -debenzoyl tashironin ( 4 ), anisatin ( 6 ), and other members. − Efficiencies of these routes have varied, from upward of 40 steps to 6 , down to an impressive 8 steps to 2 , according to the particular structural subtype, the targeted oxidation pattern, and the synthetic strategy employed.…”
The Illicium sesquiterpenes are a family of natural products containing over 100 highly oxidized and structurally complex members, many of which display interesting biological activities. This comprehensive account chronicles the evolution of a semisynthetic strategy toward these molecules from (+)-cedrol, seeking to emulate key aspects of their presumed biosynthesis. An initial route generated lower oxidation state analogs, but failed in delivering a crucial hydroxy group in the final step. Insight gathered during these studies, however, ultimately led to a synthesis of the pseudoanisatinoids along with the allo-cedrane natural product 11-O-debenzoyltashironin.A second-generation strategy was then developed to access the more highly oxidized majucinoid compounds including jiadifenolide and majucin itself. Overall, one dozen natural products can be accessed from an abundant and inexpensive terpene feedstock. A multitude of general observations regarding site-selective C(sp 3 )-H bond functionalization reactions in complex polycyclic architectures are reported.
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