Studies of the Enantiocontrolled Synthesis of the C(10)–C(25) Subunit of Amphidinolide C

Abstract

A stereocontrolled synthesis of 28, the C(10)–C(25) component of amphidinolide C (1), has been efficiently achieved. Reaction of the dithiane component 21 with nonracemic bis­(epoxide) 19 directly affords functionalized 2,5-trans-disubstituted tetrahydrofuran 22. Propargylation is highly diastereoselective for the formation of the desired C(12)–C(13) anti stereochemistry, and the resulting terminal alkyne 25 is utilized for a regioselective syn-silylstannylation. A general strategy is illustrated for sequential replacement of stannyl and silyl substituents of the trisubstituted alkene to yield (E)-alkenyl iodide 28.

Amphidinolides F and C2: An Odyssey in Total Synthesis

“…However, amphidinolide U ( 5 ) remains slightly cytotoxic (12 and 20 μg/mL) . Because amphidinolide C, and to a lesser extent amphidinolides F, C2, or C3, possesses potential cytotoxic activity, these marine products have received a great deal of interest from organic chemists, producing numerous synthetic approaches. − Three total syntheses of amphidinolide F ( 4 ) − and two of C ( 1 ) , have been reported. Due probably to lesser bioactivity, the total synthesis of amphidinolide U ( 5 ) was scarcely studied .…”

Convergent Synthesis of the C1–C29 Framework of Amphidinolide F

“…Over the past two decades, substantial portions of all four compounds have been synthesized by the groups of Kobayashi (C1–C10; C17–C29), 4 Armstrong (C18–C29), 5 Carter (C7–C20), 6 Dai (C18–C26), 7 Ferrié (C1–C9), 8 Forsyth (C1–C9; C11–C25; C1–C14; C15–C25), 9 Mohapatra (C1–C9; C19–C34), 10 Morken (C1–C15), 11 Pagenkopf (C1–C9; C18–C34), 12 Roush (C1–C9; C11–C29), 13 Spilling (C1–C9; C18–C29; C18–C34), 14 and Williams (C10–C25). 15 These meticulous and extensive synthetic studies have culminated in the recent total syntheses of amphidinolides F and C by the groups of Fürstner and Carter 16 , 17 and the total syntheses of amphidinolides F and C2 by the group of Ferrié. 18 …”

“…The size, stereochemical complexity, and biological activities of amphidinolides F, C, C2, and C3, have made them attractive targets for total synthesis and stimulated the development of new strategies and synthetic methods that permit rapid access to key subunits found in these natural products. Over the past two decades, substantial portions of all four compounds have been synthesized by the groups of Kobayashi (C1–C10; C17–C29), Armstrong (C18–C29), Carter (C7–C20), Dai (C18–C26), Ferrié (C1–C9), Forsyth (C1–C9; C11–C25; C1–C14; C15–C25), Mohapatra (C1–C9; C19–C34), Morken (C1–C15), Pagenkopf (C1–C9; C18–C34), Roush (C1–C9; C11–C29), Spilling (C1–C9; C18–C29; C18–C34), and Williams (C10–C25) . These meticulous and extensive synthetic studies have culminated in the recent total syntheses of amphidinolides F and C by the groups of Fürstner and Carter , and the total syntheses of amphidinolides F and C2 by the group of Ferrié …”

“…, −4.0, −4.5, −4.5, −4.8; HRMS (ESI+) m/z: [M + Na] + calcd for C 27 H 56 NaO 6 Si 2 555.3508; found 555.3484.2-{(2S,3R,5R)-5-[(5S,6R)-6-Ethynyl-2,2,3,3,8,8,9,9-octamethyl-4,7-dioxa-3,8-disiladecan-5-yl]-3-methyl-tetrahydrofuran-2-yl}ethyl 2,2-dimethylpropanoate(15). Pyridine (1.09 mL, 13.5 mmol) and Dess−Martin periodinane (1.90 g, 4.48 mmol) wereThe Journal of Organic Chemistry pubs.acs.org/joc Article h i b i t e d .…”

Synthetic Studies on Amphidinolide F: Exploration of Macrocycle Construction by Intramolecular Stille Coupling

“…Amphidinolide F and related amphidinolides are alluring synthetic targets because of their structural complexity and reported biological activities. Myriad synthetic strategies for the stereoselective construction of key fragments of amphidinolide F have been explored in recent years, and many of them are also directly applicable to the synthesis of members of the amphidinolide C series because of the structural similarity of the compounds. − This work has resulted in the total syntheses of amphidinolide F by the groups of Fürstner, Carter, and Ferrié; syntheses of amphidinolides C and C2 have also been completed by these research groups.…”