The Synthesis of Naturally Occurring ()‐Calyculin A

Abstract

COMMUNICATIONSt o refine independently. A t o t d of 101 parameters were refined and cower-and C were already available,[5] the synthesis of fragment B and reactions used for the fragment B construction address a previously unsolved problem in this methodology: the stereoselective coupling of chiral fragments through the aldol reaction. ["] gcncc. b a s reached at R, = 0.042 ( R = 0.058) by using o ( F o ) -2 welghts. Further d c t u k of the crystal structure investigatlon are available on rcquect from the Dii-ector of the Cambridge Crystallographic Data Centre. 11 Union Road.

Towards the total synthesis of Calyculin C: preparation of the C13–C25 spirocyclic core

“…H NMR), by stereoselective reduction of ketone 6 using potassium superhydride. 8 MEM-protection of the resultant alcohol required a large excess of reagents and a prolonged reaction time but ultimately proceeded in 66% yield. DIBAL-H reduction of 15 efficiently furnished lactol 16.…”

“…2 This interesting biological profile combined with their complex structures made the Calyculins attractive from a synthetic point of view. Several synthetic approaches have been described, 6 leading amongst others to the total syntheses of (þ)-Calyculin A by Evans 7 and Barrett, 6 (À)-Calyculin A by Masamune, 8 (À)-Calyculin B by Smith 9 and Calyculin C by Armstrong. 10 Efforts in our group have resulted in the preparation of the C 1 -C 8 , 11 C 26 -C 32 , 12 C 33 -C 38 13 fragments of Calyculin C. Herein we describe our latest results towards the construction of the C 13 -C 25 spirocyclic fragment.…”

Calyculins and Related Marine Natural Products as Serine- Threonine Protein Phosphatase PP1 and PP2A Inhibitors and Total Syntheses of Calyculin A, B, and C

“…The first total synthesis of ent -calyculin A ( 1 ) was published by Evans et al in 1992 [ 18 ]. Two years later, Masamune et al published the first total synthesis of the natural enantiomer of 1 [ 19 ]. In 1996, the Shioiri group published a formal total synthesis of 1 [ 20 ].…”

Asymmetric Synthesis of Naturally Occuring Spiroketals

“…Caliculins A and B are naturally occurring spiroketal isolated from the marine Discodermia calyx and potent serine-threonine protein phosphatase (PP1 and PP2A) inhibitors with remarkable cell membrane permeability [ 193 ]. Evans, Masamune and Yokokawa reported the synthesis of (+)-caliculin A and its antipode (-)-caliculin A [ 194 , 195 , 196 ]. Amos B. Smith, III, et al .…”