Organic Chemistry Portal
Organic Chemistry Highlights

Monday, April 15, 2013
Tristan H. Lambert
Columbia University

Total Synthesis of C-O Ring-Containing Natural Products

Scott A. Snyder at Columbia University demonstrated (J. Am. Chem. Soc. 2012, 134, 17714. DOI: 10.1021/ja3076988) that tetrahydrofuran 1 could be readily converted to oxocane 2 by treatment with the BDSB reagent developed in his laboratory. Reduction of 2 with DIBAL-H initiated a second ring closure by mesylate displacement to form the bicycle 3, which represented a formal total synthesis of Laurefucin (4).

Andrew L. Lawrence at Australian National University found (Org. Lett. 2012, 14, 4537. DOI: 10.1021/ol302042u) that upon treatment with catalytic base, Rengyolone (6), which was prepared in one pot from phenol 5, could be converted to the natural products incarviditone (7) and incarvilleatone (8). This demonstration provides strong support for the postulated biomimetic formation of these natural products.

Shuanhu Gao at East China Normal University reported (Angew. Chem. Int. Ed. 2012, 51, 7786. DOI: 10.1002/anie.201202455) the total synthesis of (+)-Fusarisetin A (12) via biomimetic oxidation of Equisetin (10) to produce the peroxy compound 11, followed by reduction. The bicyclic carbon skeleton of Equisetin (10) was synthesized by intramolecular Diels-Alder reaction of trienyl aldehyde 9.

The ellagitannin natural product (+)-Davidiin (15) possesses a glucopyranose core with the unusual 1C4 (tetra axial) conformation due to the presence of a biaryl bridge between two of the galloyl groups. Hidetoshi Yamada at Kwansei Gakuin University constructed (Angew. Chem. Int. Ed. 2012, 51, 8026. DOI: 10.1002/anie.201203305) this bridge by oxidation with CuCl2 of 13, in which the three sterically demanding triisopropylsiloxy groups enforce the requisite tetra axial conformation.

John A. Porco, Jr. at Boston University applied (J. Am. Chem. Soc. 2012, 134, 13108. DOI: 10.1021/ja305342f) his asymmetric [3+2] photocycloaddition chemistry to the total synthesis of the aglain natural product (+)-Ponapensin (20). Irradiation of hydroxyflavone 16 with methyl cinnamate (17) in the presence of diol 18 afforded the entire core framework 19 of Ponapensin (20), which was accessed in just a few further synthetic transformations.

Finally, Silas P. Cook at Indiana University reported (J. Am. Chem. Soc. 2012, 134, 13577. DOI: 10.1021/ja3061479) a five-pot total synthesis of the antimalarial (+)-Artemisinin (25). Cyclohexenone 21 was converted by simple operations to aldehyde 22. This aldehyde was then engaged in a [4+2] cycloaddition with the silyl ketene acetal 23, to produce, after an impressive Wacker oxidation of the disubstituted olefin, bicycle 24. Conversion of 24 to Artemisinin (25) was accomplished by controlled treatment with singlet oxygen followed by treatment with acid.

T. H. Lambert, Org. Chem. Highlights 2013, April 15.