TY - JOUR

T1 - Room Temperature Synthesis of Bioactive 1,2,4-Oxadiazoles

AU - Baykov, Sergey V.

AU - Shetnev, Anton A.

AU - Semenov, Artem V.

AU - Baykova, Svetlana O.

AU - Boyarskiy , Vadim P.

N1 - Baykov, S.V.; Shetnev, A.A.; Semenov, A.V.; Baykova, S.O.; Boyarskiy, V.P. Room Temperature Synthesis of Bioactive 1,2,4-Oxadiazoles. Int. J. Mol. Sci. 2023, 24, 5406. https://doi.org/10.3390/ijms24065406

PY - 2023/3/12

Y1 - 2023/3/12

N2 - 1,2,4-Oxadiazole is an essential motif in drug discovery represented in many experimental, investigational, and marketed drugs. This review covers synthetic methods that allow the conversion of different types of organic compounds into 1,2,4-oxadiazole at ambient temperature and the practical application of the latter approaches for the preparation of pharmaceutically important molecules. The discussed methods are divided into three groups. The first combines two-stage protocols requiring the preliminary preparation of O-acylamidoximes followed by cyclization under the action of organic bases. The advantages of this route are its swiftness, high efficiency of the cyclization process, anduncomplicated work-up. However, it requires the preparation and isolation of O-acylamidoximes as a separate preliminary step. The second route is a one-pot synthesis of 1,2,4-oxadiazoles directly from amidoximes and various carboxyl derivatives or aldehydes in aprotic bipolar solvents (primarily DMSO) in the presence of inorganic bases. This recently proposed pathway proved to be highlyefficient in the field of medicinal chemistry. The third group of methods consists of diverse oxidative cyclizations, and these reactions have found modest application in drug design thus far. It is noteworthy that the reviewed methods allow for obtaining 1,2,4-oxadiazoles with thermosensitive functions and expand the prospects of using the oxadiazole core as an amide- or ester-like linker inthe design of bioactive compounds.

AB - 1,2,4-Oxadiazole is an essential motif in drug discovery represented in many experimental, investigational, and marketed drugs. This review covers synthetic methods that allow the conversion of different types of organic compounds into 1,2,4-oxadiazole at ambient temperature and the practical application of the latter approaches for the preparation of pharmaceutically important molecules. The discussed methods are divided into three groups. The first combines two-stage protocols requiring the preliminary preparation of O-acylamidoximes followed by cyclization under the action of organic bases. The advantages of this route are its swiftness, high efficiency of the cyclization process, anduncomplicated work-up. However, it requires the preparation and isolation of O-acylamidoximes as a separate preliminary step. The second route is a one-pot synthesis of 1,2,4-oxadiazoles directly from amidoximes and various carboxyl derivatives or aldehydes in aprotic bipolar solvents (primarily DMSO) in the presence of inorganic bases. This recently proposed pathway proved to be highlyefficient in the field of medicinal chemistry. The third group of methods consists of diverse oxidative cyclizations, and these reactions have found modest application in drug design thus far. It is noteworthy that the reviewed methods allow for obtaining 1,2,4-oxadiazoles with thermosensitive functions and expand the prospects of using the oxadiazole core as an amide- or ester-like linker inthe design of bioactive compounds.

KW - 1,2,4-oxadiazole

KW - room temperature

KW - base catalyzed cyclization;

KW - Oxidative cyclization

KW - amidoximes

KW - bioactive compounds

KW - Bioisosteres

UR - https://www.mdpi.com/1422-0067/24/6/5406

M3 - Article

VL - 24

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 6

M1 - 5406

ER -