Total Synthesis of Amphidinolide X by Lee - Organic …
A concise total synthesis of the cytotoxic marine natural product amphidinolide X (1) is described. A key step of the highly convergent route to this structurally rather unusual macrodiolide derivative consists of a newly developed, highly syn selective formation of allenol 6 by an iron-catalyzed ring opening reaction of the enantioenriched propargyl epoxide 5 (derived from a Sharpless epoxidation) with a Grignard reagent. Allenol 6 was then cyclized with the aid of Ag(I) to give dihydrofuran 7 containing the ()-configured quarternary sp3 chiral center at C19 of the target. The anti-configured chiral centers at C10 and C11 were formed by the palladium-catalyzed, Et2Zn-promoted addition of propargyl mesylate 12 to the functionalized aldehyde 11. The key fragment coupling at the C13−C14 bond was achieved by the “9-MeO-9-BBN” variant of the alkyl-Suzuki reaction. Finally, the 16-membered macrodiolide ring was formed by a Yamaguchi esterification/lactonization strategy.
Total Synthesis of Amphidinolide X - ResearchGate
608. "Towards the Total Synthesis of Saponaceolides. A Synthesis of cis-2,4-Disubstituted-3,3-dimethylmethylenecyclohexane", Trost, B.M.; Corte, J.R.; Gudiksen, M.S. Ang. Chem. Int. Ed. (1999) 38, 3662.
706. "Palladium Catalyzed Kinetic and Dynamic Kinetic Asymmetric Transformations of gamma-acyloxybutenolides. Enantioselective Total Synthesis of (+)-Aflatoxin B-1 and B-2a" Trost, B.M.; Toste, F.D. J. Am. Chem. Soc. (2003) 125, 3090.
Total Synthesis of Amphidinolide X - CORE
599. "The Palladium-Catalyzed Enyne Cycloisomerization Reaction in a General Approach to the Asymmetric Synthesis of the Picrotoxane Sesquiterpenes. Part I. First Generation Total Synthesis of Corianin and Formal Syntheses of Picrotoxinin and Picrotin", Trost, B.M.; Haffner, C.; Jebaratnam, D.; Krische, M.J.; Thomas, A. J. Am. Chem. Soc. (1999) 121, 6183.
Part II: towards a total synthesis of amphidinolide X.
727. "Structure Elucidation of (+)-Amphidinolide A by Total Synthesis and NMR Chemical Shift Analysis." Trost, Barry M.; Harrington, Paul E. J. Am. Chem. Soc.(2004), 126, 5028-5029.
Porino Va; Total Synthesis of Amphidinolide E and Amphidinolide E ..
843. Trost, Barry M.; Sieber, Joshua, D.; Qian, Wei; Dhawan, Rajiv; Ball, Zachary, T. "Asymmetric Total Synthesis of Soraphen A: A Flexible Alkyne Strategy." Angewandte Chemie International Edition (2009), 48, 5478-5481.
Total synthesis of amphidinolide E
878. Trost, B.M.; Yang, H.; Dong, G. “Total Syntheses of Bryostatins. Syntheses of Two Ring-Expanded Bryostatin Analogues and Development of a New-Generation Strategy to Access the C7-C27 Fragment” Chem. Eur. J., (2011), 17, accpt.
Total synthesis of amphidinolide P
Thence we embarked on a systematic screening to ﬁrst establish the substrate scope of this facile isomerization, before commencing on the application of this methodology to the syntheses of two natural products — papulacandin D and amphidinolide X.
Enantioselective Total Synthesis of (+)-Amphidinolide T1
In a microwave vial, the appropriate anthranilic acid was dissolved in DMF at room temperature. After the appropriate amine was added, the reaction mixture was heated under microwave conditions. The crude reaction was monitored via low resolution mass spectrometry and purified using reverse-phase HPLC to provide the desired product. The percent yield was calculated from the mass of the purified sample. 1H NMR was used to confirm the structure of the product.