Total Synthesis of the Phenylnaphthacenoid Type II Polyketide Antibiotic Formicamycin H via Regioselective Ruthenium-Catalyzed Hydrogen Auto-Transfer [4 + 2] Cycloaddition.
J Am Chem Soc
; 146(38): 26351-26359, 2024 Sep 25.
Article
in En
| MEDLINE
| ID: mdl-39265189
ABSTRACT
The first total synthesis of the pentacyclic phenylnaphthacenoid type II polyketide antibiotic formicamycin H is described. A key feature of the synthesis involves the convergent, regioselective assembly of the tetracyclic core via ruthenium-catalyzed α-ketol-benzocyclobutenone [4 + 2] cycloaddition. Double dehydration of the diol-containing cycloadduct provides an achiral enone, which upon asymmetric nucleophilic epoxidation and further manipulations delivers the penultimate tetracyclic trichloride in enantiomerically enriched form. Subsequent chemo- and atroposelective Suzuki cross-coupling of the tetracyclic trichloride introduces the E-ring to complete the total synthesis. Single-crystal X-ray diffraction analyses of two model compounds suggest that the initially assigned stereochemistry of the axially chiral C6-C7 linkage may require revision.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ruthenium
/
Cycloaddition Reaction
/
Anti-Bacterial Agents
Language:
En
Journal:
J Am Chem Soc
Year:
2024
Document type:
Article
Affiliation country:
United States
Country of publication:
United States