On the proposed structures and stereocontrolled synthesis of the cephalosporolides

• Sami F. Tlais and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2012, 8, 1287–1292, doi:10.3762/bjoc.8.146

• strategy for controlling the stereochemistry of oxygenated 5,5-spiroketals. The same strategy likewise enables the first stereocontrolled synthesis of cephalosporolide E, which is typically isolated and prepared admixed with its spiroketal epimer, cephalosporolide F. Keywords: cephalosporolides; chelation

• report focuses on 5,5-spiroketal lactones of the cephalosporolide and related families (Figure 2) [26][27]. Cephalosporolides E and F are co-isolated as a mixture, and previous syntheses likewise produce these compounds as a mixture in the absence of methods to control the spiro-center [28][29][30

• of zinc salts between the spiroketal oxygen and appropriately positioned hydroxyls overrides normal steric biases to guide the formation of the spiroketal. Cephalosporolide E was targeted for validation of this approach. There are three main differences between cephalosporolides E and H (Figure 2

A gold-catalyzed alkyne-diol cycloisomerization for the synthesis of oxygenated 5,5-spiroketals

• Sami F. Tlais and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2011, 7, 570–577, doi:10.3762/bjoc.7.66

• cephalosporolides. Gold(I) chloride in methanol induced the cycloisomerization of a protected alkyne triol with concomitant deprotection to give a strategically hydroxylated 5,5-spiroketal, despite the potential for regiochemical complications and elimination to furan. Other late transition metal Lewis acids were

• having been made on systems that include at least one six-membered ring [5]. 5,5-Spiroketals (m, n = 0, Figure 1), particularly oxygenated 5,5-spiroketals such as are found in the cephalosporolides (Figure 2), are the focus of this study. A variety of synthetic methods are available for the synthesis of

• -shoot of our program devoted to the synthesis of functionalized alkynes by fragmentation reactions [23][24][25][26][27], we became interested in the application of alkyne-diol cycloisomerization to the synthesis of the cephalosporolides and other oxygenated spiroketals. Our retrosynthetic analysis of