Retrosynthetic analysis for the tricyclic core 6 (ABC-ring system) of GKK1032s

March 11, 2024

• Title:       

  Retrosynthetic analysis for the tricyclic core 6 (ABC-ring system) of GKK1032s

• Image Source:

  Enantioselective synthesis of the tricyclic core of GKK1032, novel antibiotic anti-tumor agents, by employing an intramolecular Diels-Alder cycloaddition strategy

• Mark:

  Scheme 1

• Associated context:

  Our synthetic plan for the target molecule 6 is outlined in  Scheme 1. The most crucial step in this scheme is envisioned to be an intramolecular Diels–Alder (IMDA) reaction of the tetraene 7 via an endo-transition state 7A to construct the requisite tricyclic core while controlling the stereogenic centers at C3, C6, C14, and C15 in 6  (7→[7A]→6). The precursor 7 would be prepared directly by Stille-coupling of the vinyl iodide 8 and the vinyl-stannane 9. The intermediate 8 should be accessed from the methyl acetylene 10 via hydrometallation/iodination and Wittig reaction. The intermediate 10 could in turn be derived through an intermolecular Diels–Alder reaction between Kitahara–Danishefsky's diene 11 and the known enulose derivative 12.