Elatenyne is a small dibrominated natural product first isolated from Laurencia elata. The structure of elatenyne was originally assigned as a pyrano[3,2-b]pyran on the basis of NMR methods. Total synthesis of the originally proposed pyrano[3,2-b]pyran structure of elatenyne led to the gross structure of the natural product being reassigned as a 2,2'-bifuranyl. The full stereostructure of this highly flexible small molecule was subsequently predicted by Boltzmann-weighted DFT calculations of (13)C NMR chemical shifts for all 32 potential diastereomers, with the predicted structure being in accord with the proposed biogenesis outlined below. Herein we report two complementary total syntheses of elatenyne, which confirm the computer-predicted stereostructure. Additionally, the total syntheses of (E)-elatenyne and a related 2,2'-bifuranyl, laurendecumenyne B, are reported. This work has not only allowed the full structure determination of all of these natural products but also provides excellent supporting evidence for their proposed biogenesis. The total synthesis of elatenyne demonstrates that DFT calculations of (13)C NMR chemical shifts coupled with biosynthetic postulates, comprise a very useful method for distinguishing among large numbers of highly flexible, closely related molecules.
The first asymmetric total synthesis of (-)-laurefucin (1), a unique C-15 acetogenin with a 2,8-dioxabicyclo[5.2.1]decane skeleton, has been accomplished in nine steps in 31% overall yield from known oxocene 10. Highlights of the highly stereoselective synthesis include a novel organoselenium-mediated biomimetic hydroxyetherification.
The formidable challenge of incorporating a bromine substituent stereoselectively at an sp3 center was met through application of a nucleophile‐assisting leaving group (see scheme). A further highlight of the highly stereo‐, regio‐, and chemoselective synthesis of (+)‐microcladallene B was a dianion alkylation to provide the required α,α′‐anti substrate for ring‐closing metathesis. TBDPS=tert‐butyldiphenylsilyl.
Substrate-controlled asymmetric total syntheses and structure confirmation of (+)-(3E)- and (-)-(3Z)-chlorofucin [(E)-1 a and (Z)-1 a], and (+)-(3E)- and (-)-(3Z)-bromofucin [(E)-1 b and (Z)-1 b] were accomplished. Our syntheses feature as key steps haloetherification (either 'conventional' or 'one-pot organoselenium-mediated') of α,α'-trans-γ,δ-unsaturated oxocene alcohol 9 and our (E)- and (Z)-selective cross-metathesis (CM) protocols. More importantly, a rationale is provided for the strikingly different pathways followed by α,α'-trans-γ,δ-unsaturated oxocene alcohol 9 and its α,α'-cis isomer 9' in the presence of different electrophiles during the intramolecular electrophilic addition reactions.
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