Total Synthesis of the Ristocetin Aglycon
| Autor: | Datong Tang, Brendan M. Crowley, Casey Cameron Mccomas, Yoshiki Mori, Dale L. Boger |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Atropisomer
Intramolecular reaction Chemistry Stereochemistry Total synthesis General Chemistry Electrophilic aromatic substitution Ring (chemistry) Biochemistry Catalysis Anti-Bacterial Agents Colloid and Surface Chemistry Ristocetin Suzuki reaction Doxorubicin Nucleophilic aromatic substitution Nucleophilic substitution |
| Zdroj: | Journal of the American Chemical Society. 126:4310-4317 |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/ja039795a |
| Popis: | The first total synthesis of the ristocetin aglycon is described employing a modular and highly convergent strategy. An effective 12-step (12% overall) synthesis of the ABCD ring system 3 from its amino acid subunits sequentially features an intramolecular aromatic nucleophilic substitution reaction for formation of the diaryl ether and closure of the 16-membered CD ring system (65%), a respectively diastereoselective (3:1, 86%) Suzuki coupling for installation of the AB biaryl linkage on which the atropisomer stereochemistry can be further thermally adjusted, and an effective macrolactamization (51%) for closure of the 12-membered AB ring system. A similarly effective 13-step (14% overall) synthesis of the 14-membered EFG ring system 4 was implemented employing a room-temperature intermolecular S(N)Ar reaction of an o-fluoronitroaromatic for formation of the FG diaryl ether (69%) and a key macrolactamization (92%) with formation of the amide linking residues 1 and 2. The two key fragments 3 and 4 were coupled, and the remaining 16-membered DE ring system was closed via diaryl ether formation to provide the ristocetin tetracyclic ring system (15 steps, 8% overall) enlisting an unusually facile (25 degrees C, 8 h, DMF,/=95%) and diastereoselective (/=15:1) aromatic nucleophilic substitution reaction that benefits from substrate preorganization. |
| Databáze: | OpenAIRE |
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