Organic Chemistry Portal
Organic Chemistry Highlights

Monday, August 27, 2018
Douglass F. Taber
University of Delaware

Carbocyclic Construction: Lysergine (Luo), Muscone (Yeung), Aplykurodinone-1 (Qiu), Dendrowardol C (Carreira), Wortmannin (Luo), Aphanamal (Morken)

Lysergine (3), isolated from ergot fungi, is related biosynthetically to the other ergot alkaloids. Tuoping Luo of Peking University assembled 3 by the radical cyclization/fragmentation of 1 to 2 (Org. Lett. 2017, 19, 620. DOI: 10.1021/acs.orglett.6b03778).

Muscone (8), isolated from a glandular secretion of the musk deer, has been widely used in perfumery. Ying-Yeung Yeung of the National University of Singapore found that 6 efficiently brominated the tertiary allylic alcohol prepared by the addition of 5 to the inexpensive cyclotridecanone 4. Radical cyclization/fragmentation of 7 so produced then delivered 8 (Org. Lett. 2017, 19, 1422. DOI: 10.1021/acs.orglett.7b00350).

Aplykurodinone-1 (11), isolated from the sea hare Siphonota geographica, has six contiguous stereogenic centers. A key step in the synthesis of 11 by Fayang G. Qiu of the Guangzhou Institute of Biomedicine and Health was the simple thermal cyclization of the Claisen rearrangement product 9 to the secondary alcohol 10 (Org. Lett. 2017, 19, 4861. DOI: 10.1021/acs.orglett.7b02350).

Dendrowardol C (14), isolated from the orchid Dendrobium wardianum Warner, has nine contiguous stereogenic centers. After the failure of a more obvious photochemical route, Erick M. Carriera of ETH Zurich found success with the reductive cyclization of 12 to 13 (Angew. Chem. Int. Ed. 2017, 56, 10890. DOI: 10.1002/anie.201705809).

Wortmannin (17), isolated from the fungus Fusarium oxysporum, is a potent irreversible inhibitor of many phosphoinositide 3-kinases. En route to 17, Professor Luo observed clean inversion in the establishment of the cyclic quaternary center by the cyclization of the Sharpless-derived epoxide 15 to 16 (J. Am. Chem. Soc. 2017, 139, 6815. DOI: 10.1021/jacs.7b02515).

Aphanamal (21) was isolated from the medicinal plant Chromolaena laevigata. James P. Morken of Boston College developed a synthetic route to 21 based on the diastereoselective cyclization of the geminal bis(boronate) 18, followed by the trapping of the intermediate with the Eschenmoser salt 19 to give 20 (Angew. Chem. Int. Ed. 2017, 56, 11485. DOI: 10.1002/anie.201705720).

D. F. Taber, Org. Chem. Highlights 2018, August 27.