Divergent Synthesis of Pyrone Diterpenes via Radical Cross Coupling

Abstract

A divergent strategy for assembling pyrone diterpenes is presented. Capitalizing on the unique stereo- and chemoselectivity features of radical-based chemistry, the core decalin of these structures is efficiently forged using an electrochemically assisted oxidative radical polycyclization while key peripheral substituents are appended using decarboxylative radical cross couplings. In this way, access to four natural products (subglutinols A/B, higginsianin A, and sesquicillin A) is achieved in a concise and stereocontrolled fashion that is modular and amenable to future medicinal chemistry explorations.

Synthetic biology based construction of biological activity-related library of fungal decalin-containing diterpenoid pyrones

“…In addition to promising biological activities, the structural features of DDPs render them exciting targets for total synthesis [42][43][44] . Recently, excellent divergent total synthesis has been reported, which enables access to four DDPs via a common intermediate in less than twenty chemical reaction steps 45 . Nevertheless, the synthesis of diverse DDPs as well as non-natural analogues is a rather elaborate effort; and therefore, it is difficult to prepare a large collection of DDPs and expand their chemical space by chemical means.…”

Taxan trifft Propellan: Erste Totalsynthese des hochkomplexen Diterpens Canataxpropellan

“…Beiträge verschiedener Gruppen aus dem Bereich der polycyclischen Terpenoide dienen als Gradmesser für diese Entwicklungen. Die radikalischen retrosynthetischen Schnitte von Baran, veranschaulicht an der Synthese von Pyron-Diterpenen, [2] und die Radikalkaskade auf dem Weg zu Berkeleyon A von Maimone sind hierfür nur zwei Beispiele. [3] Klassische Ziele wie Pleuromutilin wurden kürzlich wieder untersucht, und es konnte zum Beispiel von Herzon [4] und Reisman [5] gezeigt werden, dass viel kürzere und effizientere Synthesewege mçglich sind.…”

Late‐Stage Diversification through Manganese‐Catalyzed C−H Activation: Access to Acyclic, Hybrid, and Stapled Peptides

“…To this end, tryptophan 3a was coupled with cysteine to deliver the ligated peptide 6. Moreover,a llylated tryptophan (Trp) derivative 3b,w hich is easily accessible in gram quantities,p roved to be av iable substrate for the nickel-catalyzed radical conjugate addition, [23] furnishing desired product 7.The user-friendly nature of our strategy was further improved by using the well-defined manganese complex MnBn(CO) 5 [Mn-I], thereby avoiding the need for additives (Scheme 2c). Computational DFT analysis on the PW6B95-D3(BJ)/def2-QZVP + COSMO//TPSS-D3(BJ)/def2-TZVP level of theory [24] provided support for af acile acetate-assisted CÀHm anganesation, along with regio-discriminating migratory insertion and b-elimination (Scheme 2d).…”