On the transition-state model for the Sharpless epoxidation of allylic alcohols bearing a stereogenic centre within the allylic position [64], we expected that levorotatory stagonolide E and L-(+)-diethyl tartrate (DET) should really form the mismatched pair, while the matched pair would result with D-(-)-DET (Scheme ten). We subjected (-)-stagonolide E towards the circumstances of a Sharpless epoxidation, using each L-(+)-DET and D-(-)-DET. As anticipated on the basis of the transition-state model, no reaction occurred following two d with L-(+)-DET, plus the starting material may very well be recovered practically quantitatively. In contrast, the use of D-(-)-DET led for the formation of an epoxide 39b in 58 yield. A comparison with the analytical data of 39b with these reported for curvulide A revealed that the NMR spectroscopic information are identical, along with the worth for the distinct rotation of 39b is reasonably close for the worth reported for the organic productBeilstein J. Org. Chem. 2013, 9, 2544?555.isomers. Nonetheless, the calculated energy-minimized structures of 39a and 39b recommend that the H5 6 dihedral angles should really differ substantially (Figure two). For 39a, this angle must be close to 90? which is not in agreement with a coupling continuous of eight.2 Hz. In contrast, the identical dihedral angle is usually anticipated to be roughly 170?within the case in the diastereomeric epoxide 39b, and this value fits well to the observed 3J(H5 six) value (Figure two) [65].5-Bromo-3-chloropyridazine structure Scheme 10: Transition-state models for the Sharpless epoxidation of stagonolide E with L-(+)-DET (left) and D-(-)-DET (ideal).(4-Chlorophenyl)(2-nitrophenyl)sulfane structure Figure two: MM2 energy-minimized structures of 39a and 39b.PMID:24856309 ([]D23 +133) [30]. Thus, we conclude that the Sharplessepoxidation product of stagonolide E is identical with curvulide A and suggest the (4R,5R,6R,9R)-configuration shown for 39b (Scheme 11). Even though the R-configuration assigned to C6 and C9 is unequivocally established, for the reason that these stereocenters originate from stagonolide E, there still remains an uncertainty for the absolute configurations at C4 and C5. While the relative trans-configuration at these stereocenters is evident from a small 3J(H4 five) value of 2.2 Hz and from the E-configuration on the precursor, the relative configuration of C6 and C5, and hence the absolute configurations at C4 and C5, can not be assigned with absolute reliability. Even so, a comparatively significant coupling constant 3J(H5 6) of 8.two Hz is pointing towards a trans-orientation of those protons with a big dihedral angle. However, we could not obtain the (4S,5S,6R,9R)-configured 39a and evaluate the critical 3J(H5 6) coupling constants on the two diastereo-ConclusionIn summary, we synthesized the naturally occurring tenmembered lactones stagonolide E and curvulide A, starting in the ex-chiral pool developing block (R,R)-hexa-1,5-diene3,4-diol. Key elements from the stagonolide E synthesis are the two-directional functionalization of your enantiopure, C2-symmetrical starting material through cross metathesis plus a oneflask ring-closing metathesis/base-induced ring-opening sequence, a Ru ipase-catalyzed dynamic kinetic resolution to establish the stereochemistry at C6, along with a Yamaguchi macrolactonization. The very first synthesis of curvulide A was accomplished by Sharpless epoxidation of stagonolide E. While the previously assigned absolute and relative configurations of stagonolide E may be confirmed by the synthesis described herein, we have been in a position to supply extra data concerning missing structural assignments for.