Total Synthesis of Calyculin C

• Published in: Journal of the American Chemical Society Vol. 120; no. 48; pp. 12435 - 12442
• Main Authors: Ogawa, Anthony K, Armstrong, Robert W
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 09.12.1998; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Multidisciplinary; Physical Sciences; Science & Technology; TYPE-2A PROTEIN PHOSPHATASES; POTENT INHIBITOR; ASYMMETRIC-SYNTHESIS; DIASTEREOFACIAL SELECTIVITY; CONSTRUCTION; SPIROKETAL FRAGMENT; SPONGE DISCODERMIA-CALYX; BIOACTIVE MARINE METABOLITES; STEREOCONTROLLED SYNTHESIS; STEREOSELECTIVE SYNTHESIS
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja980836q

The study of phosphatases continues to flourish given their prominence in signal transduction pathways and the regulation of cell function. Our research efforts in this area focus on the potent inhibition of serine/threonine phosphatases, PP1 and PP2A, by a structurally diverse class of natural products. We herein report the completed total synthesis of the serine/threonine phosphatase inhibitor calyculin C (1) as part of an ongoing effort to elucidate key structural requirements for phosphatase inhibition by the aforementioned diverse class of natural products. Synthetic issues addressed include (1) the remote protecting group effect on Brown crotylboration diastereoselectivity during the introduction of the C10−C11 stereocenters and (2) the formation of the C25−C26 double bond using a fully deprotected C26−C37 phosphonium salt (3). In addition, the concurrent synthesis of 34R-calyculin C (29) clarified our previous C34-stereochemical assignment of C26−C37 phosphonium salts (3 and 27) (Ogawa, A. K.; DeMattei, J. A.; Scarlato, G. R.; Tellew, J. E.; Chong, L. S.; Armstrong, R. W. J. Org. Chem. 1996, 61, 6153).