Organic Chemistry Portal
Organic Chemistry Highlights

Monday, June 11, 2012
Douglass F. Taber
University of Delaware

Natural Product Synthesis by C-H Functionalization: (-)-Zampanolide (Ghosh), Muraymycin D2 (Ichikawa), (+)-Sundiversifolide (Iwabuchi), (+)-Przewalskin B (Zhang/Tu), Artemisinin (Wu)

Arun K. Ghosh of Purdue University exposed (Org. Lett. 2011, 13, 4108 DOI: 10.1021/ol201626h) the ether 1 to DDQ. Hydride abstraction iniated nucleophilic addition of the allyl silane, which proceeded with high diastereocontrol to deliver 2, a key intermediate in the synthesis of (+)-Zampanolide 3.

Satoshi Ichikawa, after surveying (Org. Lett. 2011, 13, 4028. DOI: 10.1021/ol201527k) several N protecting groups, settled on the phthalimide 4 as the best for directing the Du Bois oxidative cyclization. The sulfamate 5 was carried forward to a key component for the assembly of Muraymycin D2 (6).

Yoshiharu Iwabuchi of Tohoku University found (Org. Lett. 2011, 13, 3620. DOI: 10.1021/ol201273b) that the silyl diazo ester 7 cyclized with high regiocontrol, inserting with retention of absolute configuration into the H adjacent to the ether oxygen. The insertion also proceeded with high diastereocontrol, to deliver an intermediate silyl lactone that was suitably arrayed for the subsequent Peterson elimination to give 8, a key intermediate for the synthesis of (+)-Sundiversifolide 9.

Fu-Ming Zhang and Yong-Qiang Tu of Lanzhou University prepared (J. Org. Chem. 2011, 76, 6918. DOI: 10.1021/jo201111w) the α-diazo β-keto ester 10. Rh-catalyzed intramolecular C-H insertion, again with retention of absolute configuration, gave an intermediate that on deprotection cyclized to the lactone 11, only a few steps removed from (+)-Przewalskin B (12).

Yikang Wu of the Shanghai Institute of Organic Chemistry devised (Org. Lett. 2011, 13, 4212. DOI: 10.1021/ol2015434) a novel preparation for cyclic peroxides such as 13. Gentle oxidation of 13 led to 14, that was further oxidized to Artemisinin 15. Also known as Qinghaosu, 15 is the key active component of current anti-malarials.

D. F. Taber, Org. Chem. Highlights 2012, June 11.