Stereoselective Total Synthesis of (−)-Spirofungin A by Utilising Hydrogen-Bond Controlled Spiroketalisation

• Published in: Chemistry : a European journal 2011-01, Vol.17 (1), p.297-304
• Main Authors: Lynch, John E., Zanatta, Shannon D., White, Jonathan M., Rizzacasa, Mark A.
• Format: Article
• Language: English
• Subjects: Furans - chemical synthesis; Furans - chemistry; Hydrogen Bonding; hydrogen bonds; Molecular Structure; natural products; Pyrans - chemical synthesis; Pyrans - chemistry; Spiro Compounds - chemical synthesis; Spiro Compounds - chemistry; spirofungins; spiroketals; Stereoisomerism; Streptomyces - chemistry; total synthesis
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201002501

The stereoselective total synthesis of the spiroketal containing Streptomyces metabolite (−)‐spirofungin A (1) is described. A key step involved a spiroketalisation controlled by an intramolecular H‐bond which favoured the desired spiroketal 4 (13:1 ratio). The presence of the intramolecular H‐bond in 4 is possibly due to a 1,5‐alkyne–oxygen interaction. Other key steps include an efficient cross‐metathesis to form the spiroketal precursor, a tin mediated syn‐aldol reaction and a Stille cross‐coupling reaction to create the C22C23 bond. A final Wittig extension followed by deprotection gave (−)‐spirofungin A (1). Spiro key: The stereoselective total synthesis of the spiroketal‐containing Streptomyces metabolite (−)‐spirofungin A (1) is described. A key step involved a spiroketalisation controlled by an intramolecular hydrogen bond, which favoured the desired spiroketal 2 (13:1 ratio). Other key steps include an efficient cross‐metathesis to form the spiroketal precursor and a Stille cross‐coupling reaction. A final Wittig extension followed by deprotection gave 1.