Formal Syntheses of (±)-Platensimycin and (±)-Platencin via a Dual-Mode Lewis Acid Induced Cascade Cyclization Approach

Abstract

A mild and efficient dual-mode Lewis acid induced Diels-Alder (DA)/carbocyclization cascade cyclization reaction has been developed for construction of the tricyclic core of ent-kaurenoids in one pot with the aid of a theoretical study on the π,σ-Lewis acidities of a variety of Lewis acids. With ZnBr2 as the dual-mode Lewis acid, a series of substituted enones and dienes underwent DA/carbocyclization cascade cyclization reaction smoothly at room temperature and provided the tricyclic cyclized products in one pot with good yields and high diastereoselectivity. The tricyclic cyclized product has been successfully utilized as a common intermediate for formal syntheses of (±)-platensimycin and (±)-platencin.

Scalable synthesis enabling multilevel bio-evaluations of natural products for discovery of lead compounds

“…To our delight, we finally found that using the combination of Me 2 AlCl and LiBr can greatly enhance the subsequent carbocyclization step and afford 65% of (±)− 11 in a single operation. In our previous study, using Me 2 AlCl alone cannot induced carbocyclization of silyl enol ethers with alkynes 55 . There is only one successful example reported in the literature by using EtAlCl 2 as the promoter, which gave the 6- endo cyclization product 57 .…”

“…After protection of the diol as t -butyldimethyl (TBS) ethers, treatment of dichlorodicyanoquinone (DDQ) led to enone (±)− 10 in a single operation. Unfortunately, Mukaiyama–Michael/carbocyclization cascade cyclization attempts of (±)− 10 using dual-mode Lewis acids 55 , 56 (such as Zn 2+ , Fe 3+ and In 3+ ) did not give any of the expected cyclized product (±)− 11 . After a survey of a variety of strong σ-Lewis acids, we found that only Me 2 AlCl in CH 2 Cl 2 afford trace amounts of (±)− 11 along with the Michael adduct as the major side-product.…”

Review of Platensimycin and Platencin: Inhibitors of β-Ketoacyl-acyl Carrier Protein (ACP) Synthase III (FabH)

“…Again using the Lewis acid induced cascade cyclization approach to platencin, with minor modifications (Scheme 3), Zhu et al [28] synthesized the tricyclic diketone 10 , which was further converted to enone 18 by oxidation. Then, enone 18 was reduced using Luche reduction conditions to diol 19 in a single diastereomer.…”

Dinuclear versus mononuclear pathways in zinc mediated nucleophilic addition: a combined experimental and DFT study

“…[17][18][19][20][21] Almost all of these transformations are considered to proceed through a mononuclear zinc (II) mediated pathway. [22][23][24][25] For example, many ZnCl 2 , 3 ZnBr 2 , 20 ZnI 2 , 22 Zn(OTf) 2 , [11][12] Et 2 Zn, 26 and in-situ generated organozinc 2,17 promoted nucleophilic additions are proposed or proved to contain mononuclear zinc species as the key intermediates. Dinuclear zinc pathways have always been neglected because chemists are far more familiar with mononuclear zinc pathway when considering the mechanism of zinc-involved organic transformations.…”