A Vicinal Diol Approach for the Total Synthesis of Molestin E, ent‐Sinulacembranolide A and ent‐Sinumaximol A. Issue 63 (6th September 2022)

• Record Type: Journal Article
• Authors: Hoff, Oskar; Kratena, Nicolas; Aynetdinova, Daniya; Christensen, Kirsten E.; Donohoe, Timothy J.
• Is Part Of: Chemistry. Volume 28:Issue 63(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-09-06
• Subjects: cembranoids -- macrolactones -- metathesis -- natural products -- total synthesis; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202202464
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: In this work an approach for the synthesis of furanocembranoid natural products containing the C‐7, 8‐diol moiety is disclosed. This culminated in the first total synthesis of the natural product molestin E, together with ent‐sinulacembranolide A and ent‐sinumaximol A as well as a thorough exploration of their chemistry. Late‐stage ring‐closure of the C‐7, 8‐diols to the corresponding epoxides was also demonstrated. Key features of this synthetic strategy include a stereoselective Baylis‐Hillman reaction, ring‐closing metathesis and Shiina macrolactonisation. Chiral‐pool materials were deployed to ensure the desired absolute stereochemistry which was confirmed by late‐stage single crystal X‐ray diffraction. Abstract : The convergent total synthesis of furanocembranoids (FC) molestin E, ent ‐sinulacembranolide A and ent ‐sinumaximol A was achieved in 20–21 steps in the longest linear sequence (LLS). Building blocks were coupled through a furan metalation sequence and macrocycle formation was effected by Shiina lactonisation. The primary target molestin E was elaborated late‐stage to 12 novel FC compounds.