Total Synthesis of (+)-Calyculin A and (−)-Calyculin B:  Asymmetric Synthesis of the C(9−25) Spiroketal Dipropionate Subunit

• Published in: Journal of the American Chemical Society Vol. 121; no. 45; pp. 10468 - 10477
• Main Authors: Smith, Amos B, Friestad, Gregory K, Barbosa, Joseph, Bertounesque, Emmanuel, Hull, Kenneth G, Iwashima, Makoto, Qiu, Yuping, Salvatore, Brian A, Spoors, P. Grant, Duan, James J.-W
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 17.11.1999; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Multidisciplinary; Physical Sciences; Science & Technology; ENANTIOSPECIFIC SYNTHESIS; 1,3-DIOL ACETONIDES; ACYCLIC HOMOALLYLIC ALCOHOLS; IODINE MONOBROMIDE IBR; SPONGE DISCODERMIA-CALYX; LOW-TEMPERATURE; MARINE PRODUCTS CALYCULINS; STEREOCONTROLLED SYNTHESIS; STEREOSELECTIVE SYNTHESIS; OKADAIC ACID
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja992134m

An asymmetric synthesis of the stereochemically fully endowed C(9−25) spiroketal fragment (+)-BC of the calyculins (1−8) is described. Highlights of the synthesis include:  a highly diastereoselective IBr-induced iodocarbonate cyclization to introduce the C(21) stereocenter in epoxide (+)-18, fragment 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) ketone via 1,3-induction, and development of an orthogonal protection scheme permitting both convenient installation of the C(17) phosphate group and flexibility in subsequent fragment couplings.