A semisynthesis of 3'-O-ethyl-5,6-dihydrospinosyn J based on the spinosyn A aglycone

• Main Authors: Kai Zhang, Shenglan Liu, Anjun Liu, Hongxin Chai, Jiarong Li, Lamusi A
• Format: Article
• Language: English
• Published: Beilstein-Institut 2017-12-01
• Series: Beilstein Journal of Organic Chemistry
• Subjects: 3-O-ethyl-2,4-di-O-methylrhamnose; protecting groups; semisynthesis; spinetoram; spinosyn A
• Online Access: https://doi.org/10.3762/bjoc.13.257

Spinetoram, a mixture of 3'-O-ethyl-5,6-dihydrospinosyn J (XDE-175-J, major component) and 3'-O-ethylspinosyn L (XDE-175-L, minor component), is a novel kind of green and efficient insecticide with a broad range of action against various insects. Nowadays, spinetoram is widely used in agriculture and food storage. This work reports a 7-step semisynthesis of 3'-O-ethyl-5,6-dihydrospinosyn J from spinosyn A aglycone. The C9–OH and C17–OH of the aglycone are successively connected to 3-O-ethyl-2,4-di-O-methylrhamnose and D-forosamine after selective protection and deprotection steps. Then, with 10% Pd/C as catalyst, the 5,6-double bond of the macrolide was selectively reduced to afford 3'-O-ethyl-5,6-dihydrospinosyn J. In addition, the 3-O-ethyl-2,4-di-O-methylrhamnose is synthesized from rhamnose which is available commercially, while the D-forosamine and aglycone are obtained via the hydrolysis of spinosyn A. High yields were obtained in each step, and all intermediates in the synthesis were characterized by 1H NMR, 13C NMR and MS techniques. This study can be helpful for developing an efficient chemical synthesis of spinetoram, and it also offers opportunities to synthesize spinosyn analogues and rhamnose derivatives.