Asymmetric Total Synthesis of (2E)-Macrolactin 3

Abstract

Asymmetric total synthesis of (2E)-macrolactin 3 has been accomplished in a highly convergent manner utilizing our earlier developed tandem isomerization followed by C-O and C-C bond-forming Sharpless asymmetric dihydroxylation, and a late-stage intramolecular Heck coupling reaction. Comparison of the NMR spectra of the coupled product and thorough analysis of the 2D NMR data of the final compound led to the conclusion that the Z-double bond at C2 was isomerized during the coupling reaction.

Heck Macrocyclization in Forging Non-Natural Large Rings including Macrocyclic Drugs

“…As illustrated in Figure 17B, Pd-catalyzed carbonylative Heck-type macrolactonization, C-H functionalization, lactonization, and lactamization have inspiringly led to the total synthesis of spinosyn A [135], cephanolides B [136], perseanol [137], and α-schizozygol [138], respectively. With regard to large rings, shortly after a 2021 review [12], more progress was made in the total synthesis of isoriccardin C [139], pulvomycin D (Figure 17C) [140], and the (2E) isomer of macrolactin 3 [141]. The theme of the present review, on the other hand, is to raise awareness of the fact that this reaction is likewise useful in forging synthetic macrocycles, especially macrocyclic drugs.…”