Stereochemical Determination of Tuscolid/Tuscorons and Total Synthesis of Tuscoron D and E: Insights into the Tuscolid/Tuscoron Rearrangement

Abstract

The stereochemistry of the structurally unique myxobacterial polyketides tuscolid/tuscorons was determined by ac ombination of high-field NMR studies,m olecular modeling,a nd chemical derivatization and confirmed by am odular total synthesis of tuscorons Da nd E. Together with the discovery of three novel tuscorons,this study provides detailed insight into the chemically unprecedented tuscolid/ tuscoron rearrangement cascade.

Total Synthesis of Pentamycin by a Conformationally Biased Double Stille Ring Closure with a Trienyl-bis-stannane

“…The primary hydroxyl function was then exchanged to a chlorine under Appel conditions, and a double-elimination reaction using n-BuLi gave desired propargylic alcohol 12 in excellent yield. 26,27 After protection of the secondary hydroxyl as a TBS ether, the alkyne was converted to vinyl iodide 13 using Cp 2 ZrCl 2 -DIBAL-H according to a procedure of Huang and Negishi. 28 Finally, treatment with DDQ to remove the PMB protecting group gave desired fragment 7.…”

“…Best results were obtained with Masamune Roush conditions using triethylphosphono acetate ( 9 ) in the presence of LiCl and DIPEA giving enoate 10 with high ( E )-selectivity of 50:1. , For conversion to propargylic alcohol 12 , a procedure of Gonela et al (2018) was applied, which involved first reduction to the corresponding allylic alcohol with DIBAL-H and subsequent Sharpless asymmetric epoxidation yielding epoxide 11 with a good selectivity (25:1). The primary hydroxyl function was then exchanged to a chlorine under Appel conditions, and a double-elimination reaction using n -BuLi gave desired propargylic alcohol 12 in excellent yield. , After protection of the secondary hydroxyl as a TBS ether, the alkyne was converted to vinyl iodide 13 using Cp 2 ZrCl 2 -DIBAL-H according to a procedure of Huang and Negishi . Finally, treatment with DDQ to remove the PMB protecting group gave desired fragment 7 …”