Design and Synthesis of C-1 Methoxycarbonyl Derivative of Narciclasine and Its Biological Activity
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis of the A-Ring Coupling Precursor
2.2. Enzymatic Dihydroxylation of ortho-Dibromobenzene and Nitroso Diels–Alder Reaction
2.3. C–1 Functionalization via Pd-Catalyzed Carbonylation
2.4. Intramolecular Heck Reaction and Global Deprotection to Afford 1-Methoxycarbonyl Narciclasine
2.5. Biological Activity
3. Materials and Methods
3.1. General Information
3.2. Preparation and Characterization of Compounds
3.2.1. (3aS,4S,7R,7aS)-Benzyl-4,5-dibromo-2,2-dimethyl-3a,4,7,7a-tetrahydro-4,7-(epoxyi-mino)benzo[d][1,3]dioxole-8-carboxylate (21)
3.2.2. ((3aS,4R,7R,7aR)-Benzyl-6-bromo-7-hydroxy-2,2-dimethyl-3a,4,7,7a-tetrahydroben-zo[d][1,3]dioxol-4-yl)carbamate (22)
3.2.3. ((3aS,4R,7R,7aS)-Benzyl-6-bromo-7-((tert-butyldimethylsilyl)oxy)-2,2-dimethyl-3a,4,7,7a-tetrahydrobenzo[d][1,3]dioxol-4-yl)carbamate (23)
3.2.4. (3aS,4S,7R,7aS)-Methyl 7-(((benzyloxy)carbonyl)amino)-4-((tert-butyldimethylsilyl) oxy)-2,2-dimethyl-3a,4,7,7a-tetrahydrobenzo[d][1,3]dioxole-5-carboxylate (24)
3.2.5. (3aS,4S,7R,7aS)-Methyl-7-(6-bromo-4-methoxybenzo[d][1,3]dioxole-5-carboxamido) -4-((tert-butyldimethylsilyl)oxy)-2,2-dimethyl-3a,4,7,7a-tetrahydrobenzo[d][1,3]dioxole-5 -carboxylate (27)
- Step A: Preparation of acid chloride 14
- Step B: Preparation of primary amine 11
- Step C: Condensation of amine 11 with acid chloride 14 to afford compound 27
3.2.6. (3aS,4S,7R,7aS)-Methyl-7-(6-bromo-N-(tert-butoxycarbonyl)-4-methoxybenzo[d][1,3] dioxole-5-carboxamido)-4-((tert-butyldimethylsilyl)oxy)-2,2-dimethyl-3a,4,7,7a-tetrahyd-robenzo[d][1,3]dioxole-5-carboxylate (28)
3.2.7. 4-(tert-Butyl)-11-methyl(3aS,3bR,12S,12aS)-12-((tert-butyldimethylsilyl)oxy)-6-met-hoxy-2,2-dimethyl-5-oxo-3a,5,12,12a-tetrahydrobis([1,3]dioxolo)[4,5-c:4’,5’-j]phenanthrid-ine-4,11(3bH)-dicarboxylate (29)
3.2.8. (3aS,3bR,12S,12aS)-Methyl-12-((tert-butyldimethylsilyl)oxy)-6-hydroxy-2,2-dimet-hyl-5-oxo-3a,3b,4,5,12,12a-hexahydrobis([1,3]dioxolo)[4,5-c:4’,5’-j]phenanthridine-11-car-boxylate (30)
3.2.9. (2S,3R,4S,4aR)-Methyl-2,3,4,7-tetrahydroxy-6-oxo-2,3,4,4a,5,6-hexahydro-[1,3]diox-olo [4,5-j]phenanthridine-1-carboxylate (10)
3.3. Cell Viability Assay
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
References
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Habaz, L.; Bedard, K.; Smith, M.; Du, L.; Kornienko, A.; Hudlicky, T. Design and Synthesis of C-1 Methoxycarbonyl Derivative of Narciclasine and Its Biological Activity. Molecules 2022, 27, 3809. https://doi.org/10.3390/molecules27123809
Habaz L, Bedard K, Smith M, Du L, Kornienko A, Hudlicky T. Design and Synthesis of C-1 Methoxycarbonyl Derivative of Narciclasine and Its Biological Activity. Molecules. 2022; 27(12):3809. https://doi.org/10.3390/molecules27123809
Chicago/Turabian StyleHabaz, Lihi, Korey Bedard, Mitchell Smith, Liqin Du, Alexander Kornienko, and Tomas Hudlicky. 2022. "Design and Synthesis of C-1 Methoxycarbonyl Derivative of Narciclasine and Its Biological Activity" Molecules 27, no. 12: 3809. https://doi.org/10.3390/molecules27123809