An expedient synthesis of spiroketals: model studies for the calyculin C16–C25 fragment
Abstract A new short strategy to prepare the spiroketal fragment of calyculins is presented. A novel Seyferth–Gilbert type homologation of hindered lactols to the corresponding alkynes has been achieved for the first time. The spirocyclization was achieved efficiently via a DIHMA (double intramolecular hetero-Michael addition) process of this hindered ynone. The spirocyclization rate is not dependent on the stereochemistry of the alkoxy substituent in the oxolane ring.
The Reaction Mechanism of Spirocylization and Stereoselectivity Studies for the Calyculin C16-C25 Fragment
The mechanism of the double intramolecular hetero-Michael addition, a key reaction in the planned synthesis of the natural product calyculin C, has been studied by NMR. The cyclization follows Baldwin’s rules and proceeds first through a six-membered ring closure (6-endo-dig), followed by a five-membered ring cyclization (5-exo-trig). (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Absolute Stereochemistry of the Calyculins, Potent Inhibitors of Protein Phosphatases 1 and 2A☆
Abstract A mixture of calyculins A, B, E, and F, which are geometric isomers at Δ 2 and Δ 6 , was subjected to acid hydrolysis to obtain 2,3-dihydroxy-4-dimethylamino-5-methoxypentanoic acid ( 3 ), corresponding to the C33–C37 portion of the calyculins. A positive Cotton effect at 207 nm in the CD spectrum indicated 2 S stereochemistry for 3 , or 34 S for the calyculins, thereby establishing the absolute configuration of the calyculins.