spirastrellolide-b and dithiane

The spirastrellolides are a family of potent antimitotic agents isolated from the marine sponge Spirastrella coccinea . Synthetic studies toward the DEF bis-spiroacetal core of spirastrellolide B are reported. A modular approach was pursued by the use of two dithiane disconnections to enable a highly convergent synthesis. The ease of lithiation and nucleophilicity of these 2-substituted-1,3-dithianes were investigated during the course of the synthesis, and the alkylations were found to proceed most efficiently at elevated temperatures. Formation of the [5,6,6]-bis-spiroacetal ring system was achieved via a double dithiane deprotection/spiroacetalization strategy.

Topics: Alkylation; Antimitotic Agents; Biological Products; Macrolides; Molecular Structure; Quinolizines; Spiro Compounds; Sulfur Compounds

Use of a bis-dithiane deprotection-tandem bis-spiroacetalisation sequence was key to the successful synthesis of the [5,6,6]-bis-spiroacetal of the antimitotic agent spirastrellolide B, achieved in a highly convergent fashion involving successive dithiane alkylations.

Topics: Alkylation; Antimitotic Agents; Macrolides; Protein Phosphatase 2; Quinolizines; Spiro Compounds; Sulfur Compounds