Novel stereocontrolled approach to syn- and anti-oxepene-cyclogeranyl trans-fused polycyclic systems: asymmetric total synthesis of (-)-Aplysistatin, (+)-Palisadin A, (+)-Palisadin B, (+)-12-hydroxy-palisadin B, and the AB ring system of adociasulfate-2 and toxicol A.
A new stereocontrolled method for the formation of trans-anti cyclogeranyl-oxepene systems is described. The demanding stereochemistry is secured by stereoselective coupling of a cyclogeranyl tertiary alcohol with a 1,2-unsymmetrically substituted epoxide, while the formation of the highly strained oxepene is achieved employing ring-closing metathesis. Since the stereochemistry of the trans-fused 6,7-ring system is determined by the epoxide, the method also allows the construction of trans-syn 6,7-ring systems. This approach leads to the synthesis of the AB fragment of Adociasulfate-2 and Toxicol A, for the first time. The flexibility and efficiency of the presented strategy is demonstrated by the total asymmetric synthesis of (-)-Aplysistatin, (+)-Palisadin A, (+)-12-hydroxy-Palisadin B, and (+)-Palisadin B, employing two similar key intermediates.
Couladouros
Elias A
EA
Chemistry Laboratories, Agricultural University of Athens, Iera Odos 75, Athens 118 55, Greece. ecoula@chem.demokritos.gr
Vidali
Veroniki P
VP
D003500:Cyclization; D004852:Epoxy Compounds / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D010082:Oxepins / Q000138:chemical synthesis*; D012717:Sesquiterpenes / Q000138:chemical synthesis*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013463:Sulfuric Acid Esters / Q000138:chemical synthesis*
D004852:Epoxy Compounds; D010082:Oxepins; D012717:Sesquiterpenes; D013463:Sulfuric Acid Esters; C111568:adociasulfate-2; C013402:aplysistatin