Total synthesis and stereochemical revision of relgro and 10′-oxorelgro

Abstract

The first total synthesis and correct stereochemical assignments of relgro (6′S,10′S)-configuration and 10′-oxorelgro with (6′S)-configuration are described.

First Total Synthesis of Gaylussacin and Its Stilbene Derivatives

“…5,7-Dihydroxy-2,2-dimethyl-4H-benzo [d][1,3]dioxin-4-one (9). 6 To a stirred solution of 2,4,6-trihydroxybenzoic acid monohydrate 8 (4.0 g, 21.26 mmol) in trifluoroacetic acid (37.4 mL, 488.9 mmol), trifluoroacetic anhydride (25.1 mL, 180.7 mmol) and acetone (11.7 mL, 170 mmol) were added at 0 °C under argon atmosphere. The mixture was warmed slowly to room temperature (rt) and stirred for 20 h. After completion of the reaction, the mixture was concentrated under reduced pressure with toluene (3 × 200 mL).…”

“…As outlined in Scheme , the ketal group was fixed first for the protection of the carboxylic acid and the neighboring phenol, as late stage removal can liberate the free carboxylic acid and phenol in one step. In the presence of acetone, TFA, and TFAA, ketal protection of 8 was conducted, and protected product 9 was obtained in 60% yield . For the selective protection of the 4-phenol group from 9 , we investigated various protecting groups, such as benzyl, TBS, MOM, and benzoyl.…”

“…In the presence of acetone, TFA, and TFAA, ketal protection of 8 was conducted, and protected product 9 was obtained in 60% yield. 6 For the selective protection of the 4-phenol group from 9, we investigated various protecting groups, such as benzyl, TBS, MOM, and benzoyl. The benzyl group was excluded, because hydrogenation of unsaturated π-bonds in the stilbene intermediate 6c would be problematic during its cleavage step.…”

Metathesis Reactions in Natural Product Fragments and Total Syntheses

“…Mohapatra and teammates accomplished the first asymmetric total synthesis of the (6′ R ,10′ S )‐relgro 206 (Scheme 15), a 10‐membered β ‐resorcylic macrolide extracted from fungus Fusarium sp . PSU‐ES73 [194] . To this journey, total 9 steps were utilized, whereas RCM was one of the decisive steps employed in late‐stage to construct the 10‐membered lactone.…”

“…PSU-ES73. [194] To this journey, total 9 steps were utilized, whereas RCM was one of the decisive steps employed in latestage to construct the 10-membered lactone. Esterification of a chiral alcohol 203 with aromatic acid 202 in presence of EDCI/ DMAP resulted in the formation of a diene 204, which upon RCM with G-II catalyst delivered a 10-membered macrolactone 205 in 80% yield.…”