A Vicinal Diol Approach for the Total Synthesis of Molestin E, ent‐Sinulacembranolide A and ent‐Sinumaximol A

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 entsinulacembranolide A and ent-sinumaximol A as well as a thorough exploration of their chemistry. Late-stage ringclosure 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 Xray diffraction.

Studies toward Providencin: The Furanyl-Cyclobutanol Segment

“… − It is the massive ring strain that presents the biggest challenge; this notion is best appreciated if one triesto no availto build a Dreiding model of the compound . The 7,8- trans epoxide (or the corresponding E -alkene precursor) , is arguably the single most stiffening substructure, closely followed by the cyclobutyl alcohol trans -annulated to the macrocyclic frame.…”

Marine natural products

“…531 Both biscembranoids were inactive in testing for anti-inflammatory responses related to superoxide anion or elastase release from induced human neutrophils. First syntheses of cembranoid MNPs molestin E, 532 (+)-ineleganolide and (−)-sinulochmodin C, 533 and scabrolide F 1366 have been reported, with the latter study establishing the absolute configuration of the molecule. 534 The structure assigned to scabrolide B has been called into question as the result of a total synthesis of the purported structure.…”

Exploring the synthetic potential of epoxide ring opening reactions toward the synthesis of alkaloids and terpenoids: a review

“… 17 Vinyl epoxides are important synthetic precursors in organic synthesis 18 as they lead towards the synthesis of (−)-(4 R ,5 R )-Muricatacin (a natural acetogenin) via regio or stereoselective ring opening reaction of epoxide. 19 Syntheses of numerous biological active compounds such as Sphingofungin, 20 Zoanthenol, 21 marine ladder polyethers, 22 Zampanolide, 23 epi -Muscarine, 24 Molestin E, 25 (−)-Epicoccin G and (−)-Rostratin A, 26 homoisoflavonoids, 27 Chlorotonils, 28 Lingzhiol, 29 Phomarol, 30 Isoandrographolide, 31 Citrinadins, 32 Isosilybin, 33 polyester, 34 Mupirocin 35 and Bisfuranoxide 36 etc. have been accomplished by involving epoxide chemistry.…”