Synthesis of platencin core structures via twist-brendane

Faiz Ahmed Khan,Basavaraj M Budanur,Ramaiah Muthyala

doi:10.3998/ark.5550190.p009.333

Abstract

The formation of a twist-brendane via intramolecular enolate alkylation is described. Conversion of bicyclo[2.2.1]heptane scaffold present in this twist-brendane through a Grob-type fragmentation to unravel a functionalized bicyclo[2.2.2] system which contains all the necessary carbon atoms of the lipophilic core structure of nor -platencin, a platencin analogue is presented. Synthesis of core structure of platencin was also accomplished by extending this strategy to a starting material possessing a surrogate for the exocyclic methylene group.

Highlights

In this paper we report synthesis of platencin core structures which features the construction of tricyclic core via a twistbrendane derivative, followed by Grob-type fragmentation and Robinson annulation
During the course of our studies on base mediated bridgehead elimination and substitution reactions,[36] we observed the formation of a twist-brendane derivative 5 through intramolecular enolate alkylation in 70% yield along with the originally intended product 6 from 4 (Scheme 1)
Synthesis of the parent twist-brendane[5] has been described in the literature by intramolecular enolate alkylation using NaH in DMF at 60 °C followed by deoxygenation

Summary

Introduction

Intramolecular enolate alkylation has been a key step for stereoselective construction of cycloalkanes in the total synthesis of natural products of modest complexity,[1,2,3,4] and in the synthesis of strain free tricyclononane like twist-brendane.[5,6,7,8] The synthesis of natural products involving the Grob fragmentation reaction, a reliable synthetic tool for the cleavage of C‒C sigma bond leading to useful building blocks, as a key step has been gaining much attention in recent past due to its high efficiency and stereoselectivity.[9,10,11,12,13]As a novel potent antibiotic, platencin[14,15] inhibits two proteins essential for bacterial fatty acid biosynthesis, β-ketoacyl carrier protein synthase II (FabF) and III (FabH) with similar potency. The reaction mixture was diluted with EtOAc (150 mL), organic phase was separated, aqueous phase was extracted with EtOAc (100 mL x 3) combined organic phase was washed with 10% Na2CO3 solution (30 mL), water (100 mL x 2), brine (60 mL), dried over Na2SO4 and concentrated under reduced pressure.

Results

Conclusion