Total Synthesis of Pulvomycin D

Abstract

A synthetic route to the pulvomycin class of natural products is presented, which culminated in the first synthesis of a pulvomycin, pulvomycin D. Key elements of the strategy include a pivotal aldol reaction which led to bond formation between the C24‐C40 and the C8‐C23 fragment. The remaining C1‐C7 fragment was attached by a Yamaguchi esterification completing the assembly of the 40 carbon atoms within the main skeleton. Ring closure to the 22‐membered lactone ring was achieved in the final stages of the synthesis by a Heck reaction. The completion of the synthesis required the removal of six silyl protecting groups in combination with olefin formation at C26‐C27 by a Peterson elimination.

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.…”