Total Synthesis and Structure Confirmation of Elatenyne: Success of Computational Methods for NMR Prediction with Highly Flexible Diastereomers

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 13C 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 13C
NMR chemical shifts coupled with biosynthetic postulates, comprise
a very useful method for distinguishing among large numbers of highly
flexible, closely related molecules.