Synthese von Apoptolidinon

Abstract

Eine CuI‐vermittelte Kupplung der Nord‐ und der Südhälfte sowie eine ringgrößenselektive Makrolactonisierung sind die Schlüsselschritte der konvergenten, ersten Totalsynthese von Apoptolidinon (die Wellenlinien in der Formel geben die retrosynthetischen Schnitte an), dem Aglycon des potentiellen Tumortherapeutikums Apoptolidin.

Copper‐Catalyzed Asymmetric Allylic Alkylation of Halocrotonates: Efficient Synthesis of Versatile Chiral Multifunctional Building Blocks

“…The propionate building blocks have been used previously for the syntheses of (À)-a-multistriatin [33c] and apoptolidinone. [37] Finally, when the deprotected b,g-unsaturated carboxylic acid (S)-11 was subjected to iodolactonization using Barluengas reagent [38,39] the 5-membered lactone [Scheme 6, Eq. (b)] was obtained albeit in a low yield.…”

Total Synthesis of Apoptolidin

“…The synthesis of the glycosylated southern half made use of the bis(TES) ether 31 from the aglycone synthesis (Scheme 5). [9] Selective deprotection of the 27-O-TES group in 31 gave 32, which was allowed to react with the disaccharide glycal 17 to produce the glycoconjugate 33 with a high a-selectivity of > 95:5. [17] Reductive removal of the auxiliary iodo function led to the benzyl ether 34.…”

“…[6] The noticeable biological activity of apoptolidin (1) and its structural challenges make it a prominent synthetic target. [7,8] In continuation of our synthesis of the aglycon apoptolidinone [9] we communicate here the completion of the total synthesis of apoptolidin.…”

“…The synthesis of the glycosylated northern half used the unsaturated ester 26 [9] from the aglycone synthesis as a common building block (Scheme 4). Ester 26 was converted into the glycosyl acceptor 27.…”

cineSubstitution and the Cu Effect in Stille Cross‐Coupling Reactions: Mechanistic Perspectives and Synthetic Utility

“…Initial attempts at Pd 0 ‐catalyzed Stille coupling between 103 and 104 (Scheme ) were disappointing (<30 % yields at prolonged reaction times and 60 °C). In contrast, the use of two equivalents of CuTC gave 105 in 80 % yield under very mild conditions (–10 °C, 1 h) 46…”