11-Step Total Synthesis of (−)-Maoecrystal V

Abstract

An expedient, practical, and enantioselective route to the highly congested ent-kaurane diterpene maoecrystal V is presented. This route, which has been several years in the making, is loosely modeled after a key pinacol shift in the proposed biosynthesis. Only 11 steps, many of which are strategic in that they build key skeletal bonds and incorporate critical functionalities, are required to access (−)-maoecrystal V. Several unique and unexpected maneuvers are featured in this potentially scalable pathway. Reevaluation of the biological activity calls into question the initial exuberance surrounding this natural product.

Synthesis of α,ω‐Bis‐Enones by the Double Addition of Alkenyl Grignard Reagents to Diacid Weinreb Amides

“…2,2‐Dimethylcyclohexanone (7) . 2‐Methylcyclohexanone (39.3 g, 350 mmol) was methylated following a literature procedure . A mixture of 7 , 2,6‐dimethylcyclohexanone, 2,2,6‐trimethylcyclohexanone, and 2,2,6,6‐tetramethylcyclohexanone was received (>99 %).…”

“…2-Methylcyclohexanone (39.3 g, 350 mmol) was methylated following a literature procedure. [24] A mixture of 7, 2,6-dimethylcyclohexanone, 2,2,6-trimethylcyclohexanone, and 2,2,6,6-tetramethylcyclohexanone was received (>99 %). Ketone 7 and unreacted 2-methylcyclohexanone were then separated from the other polymethylated ketones following a literature procedure consisting of a selective formylation, an acid-base extraction, and a deformylation.…”

Total Synthesis of an Atropisomer of the Schisandra Triterpenoid Schiglautone A

“…Upon subjection to af reshly prepared DMDO solution, the iodine atom could be oxidized to give aputative a-iodoso species,w hich then underwent as pontaneous elimination to afford 23 in 63 %y ield. [20] After removal of the benzyl group at C3 by DDQ,t he next task required ar egioand diastereoselective reduction of the ketone at C12 in the presence of the other two ketones at C8 and C13. Among the numerous reducing conditions examined, we found that only under Luche conditions at À78 8 8Cw as the desired a-alcohol 24 obtained as am ajor diastereomer (50 %, 2s teps), accompanied by the hemiketal 25 and furanyl aldehyde 27 in 15 %and 13 %yield, respectively.Afurther reduction of 25 on C13 ketone followed by vinylogous Grob fragmentation [21] induced aromatization of 26 was presumably responsible for the formation of 27.F inally,d esilylation of 24 with TBAF uneventfully furnished 28 in 78 %y ield.…”

Chemoenzymatic Synthesis of O‐Containing Heterocycles from α‐Diazo Esters

“…Chiral oxygen-containing heterocycles are commonly found motifs in various natural products and many biologically active molecules. [1] Prominent examples include Maoecrystal V [2] , Heliannuol C [3] and the structural more complex Brevetoxins. [4] In recent years, several strategies for the diastereoselective and enantioselective construction of these important heterocycles have been developed.…”