Concise Synthesis of (−)-GA₁₈ Methyl Ester

Abstract

Gibberellins (GAs) are important plant hormones, but some of their family members are in extremely limited natural supply including GA18. Herein, we report a concise synthesis of (−)-GA18 methyl ester, a member of the C20 gibberellins, from commercially available and cheap andrographolide. Our synthesis features an intramolecular ene reaction to form the C ring, an oxidative cleavage followed by aldol condensation to realize a ring contraction and form the challenging trans-hydrindane (AB ring), and a photochemical [2+2] cycloaddition accompanied by a subsequent SmI2-mediated skeletal rearrangement to construct the methylenebicyclo[3.2.1]octanol moiety (CD ring).

Divergent Total Syntheses of Illicium Sesquiterpenes through Late-Stage Skeletal Reorganization

“…Third, a unified and efficient approach to Illicium sesquiterpenes with low to high oxidation levels in a high redox- and step-economy manner is still highly desirable. Maimone and co-workers achieved concise collective semisyntheses of a group of seco -prezizaane sesquiterpenes from (+)-cedrol through oxidative skeletal rearrangement and diverse late-stage oxidations. − As part of our continuous efforts to address these issues, , we herein report a unified, bioinspired synthesis of Illicium sesquiterpenes across seco -prezizaane, allo -cedrane, and anislactone types, featuring late-stage divergent skeletal reorganizations − triggered by either Lewis acids or oxidants and programmed oxidation level enhancements.…”

Bioinspired Skeletal Reorganization Approach for the Synthesis of Steroid Natural Products

“…Two key transformations typically must be accomplished: (1) site-selective C–H oxidation to install the required functional groups at specific positions and (2) more importantly, controlled skeletal reorganization to rapidly access the core framework of the target molecules from the 6/6/6/5-tetracyclic skeleton of classical steroids. In this Account, we summarize the evolution of our bioinspired skeletal reorganization (BSR) approach for the synthesis of SNPs, which allowed us to accomplish concise and scalable syntheses of rearranged steroids 1 – 5 .…”

9-Step synthesis of (−)-larikaempferic acid methyl ester enabled by skeletal rearrangement

“…The NMR, Mass Spec, and optical rotation data of our synthetic sample matched well with the ones reported for the natural sample. In summary, using a skeletal rearrangement 20 and transannular cyclization strategy, 21,22 we developed an efficient synthesis of (À)-larikaempferic acid methyl ester from abietic acid. The key steps include an oxidative C8-C9 double bond cleavage to deliver a 10-membered diketone, a chelation-controlled transannular aldol cyclization to build the trans 5,7-fused ring system, and an oxa-Michael addition to form the oxabicyclo[3.2.1]octane.…”