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Total Synthesis of the Natural Herbicide MBH‐001 and Analogues
Author(s) -
Kuhn Birgit,
Barber David M.,
Dietrich Hansjörg,
Döller Uwe,
Hoffmann Michael G.,
Schmutzler Dirk,
Schnatterer Stefan,
Maier Martin E.,
Kocakaya Tamer,
Morkunas Marius
Publication year - 2020
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202000294
Subject(s) - chemistry , imine , nitrone , aldehyde , total synthesis , aldol reaction , substituent , oxime , combinatorial chemistry , stereochemistry , organic chemistry , cycloaddition , catalysis
The first total synthesis of the natural herbicide MBH‐001 ( 1 ) is reported. Structurally it is a 2‐methyloxazol‐5(2 H )‐one with a (1‐hydroxyethyl) substituent at the 2‐position. By relying on cyclic nitrones, a flexible route to MBH‐001 and relevant analogues was developed. Key steps include the reaction of a 2‐hydroxyimino ester with an aldehyde to form a 5‐oxo‐2,5‐dihydrooxazole 3‐oxide. In an aldol‐type reaction, the anion of these cyclic nitrones reacted with an aldehyde at the 2‐position. A final reduction of the nitrone to the corresponding imine using zinc led to the target compounds. The cyclic nitrones are also accessible by reacting an α‐keto acid with an oxime. These two versatile synthetic routes enabled us to prepare the first MBH‐001 analogues for structure activity relationship analysis of the herbicidal efficacy. Thus, furthering our aim of developing new herbicides to tackle the ever‐growing problem of weed resistance.