Total Synthesis of (±)-Cafestol: A Late-Stage Construction of the Furan Ring Inspired by a Biosynthesis Strategy

Abstract

An efficient bioinspired approach to the total synthesis of (±)-cafestol features a late-stage installation of the furan ring with a mild Au-catalyzed cycloisomerization. The Et2AlCl-promoted aldehyde-ene cyclization and subsequent Friedel-Crafts reaction deliver a requisite tricyclic system in gram scale with high stereo- and regioselectivity. Moreover, a highly stereoselective SmI2-mediated aldehyde-alkene radical cyclization furnishes the key bicyclo[3.2.1]octane skeleton to offer an advanced intermediate for the synthesis of other oxygenated ent-kaurene diterpenoids.

Highly efficient mesoporous polymer supported phosphine-gold(i) complex catalysts for amination of allylic alcohols and intramolecular cyclization reactions

“…Furans are important intermediates, which widely serve as key structural subunits in numerous natural products, industrial organic syntheses and material science. [61][62][63] The reaction of propargyl alcohol 9 afforded the corresponding substituted furan 10 at 92% yield aer 6 h, which shows similar activity to the homogeneous catalyst (Scheme 2).…”

Advanced in the Synthesis of Kaurane Diterpenoids

“…Cafestol 是二萜衍生物, 洪然小组 [46] 提出这一分子 图式 30 洪然组的(±)-Cafestol 合成工作 Scheme 30 Hong's synthesis of (±)-cafestol…”

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

“…The chemical synthesis can be an alternative for the delivery of simpler isoprenoid structures such as carotenoids [12]. Industrially relevant total synthesis of highly oxygenated terpenes comprising several chiral centers is often more complex since usually various different reaction steps have to be performed that regularly involve cost- and workup-intensive metal-organic catalysts [13–16]. The work of McKerrall et al on ingenol [17–18] sets an example for the difficulty of stereoselective synthesis of complex diterpenes.…”