Synfacts 2016; 12(05): 0441
DOI: 10.1055/s-0035-1562026
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of (±)-Hippolachnin A

Erick M. Carreira
Leonardo J. Nannini
McCallum ME, Rasik CM, Wood JL, * Brown MK. * Baylor University, Waco and Indiana University, Bloomington, USA
Collaborative Total Synthesis: Routes to (±)-Hippolachnin A Enabled by Quadricyclane Cycloaddition and Late-Stage C–H Oxidation.

J. Am. Chem. Soc. 2016;
138: 2437-2442
Further Information

Publication History

Publication Date:
18 April 2016 (online)



In this work, the authors combine their independently elaborated routes into a unique collaborative total synthesis of (±)-hippolachnin A. The convergent synthesis relies on a [2+2] quadricyclane cycloaddition, followed by ring-opening metathesis and allylic C–H oxidation.



Thermal [2+2] cycloaddition of acyl chloride A and quadricyclane B generated cyclobutane C after treatment with sodium hydroxide in moderate yield and excellent diastereoselectivity. Ring-opening metathesis catalyzed by Grubbs I under an ethylene atmosphere gave carboxylic acid D. A late stage C–H oxidation of bicycle D gave lactone F, which was converted in three further steps into (±)-hippolachnin A.