Total synthesis of (+)-calyculin A and (-)-calyculin B: Asymmetric synthesis of the C(9-25) spiroketal dipropionate subunit

An asymmetric synthesis of the stereochemically fully endowed C(9-25) spiro ketal fragment (+)-BC of the calyculins (1-8) is described. Highlights of t he synthesis include: a highly diastereoselective IBr-induced iodocarbonate cyclization to introduce the C(21) stereocenter in epoxide (+)-18, fragmen t unions exploiting the reaction of acyl anion equivalents with epoxides to construct masked advanced aldols (-)-35 and (+)-71 as single diastereomers , chelation-controlled addition of the C(14-15) vinyl group to aldehyde (+) -38 to set the stereogenicity at C(16), selective reduction of the C(13) ke tone via 1,3-induction, and development of an orthogonal protection scheme permitting both convenient installation of the C(17) phosphate group and fl exibility in subsequent fragment couplings.