Recent Advances in the Synthesis of Tamoxifen and Analogues in Medicinal Chemistry

Abstract

Tamoxifen is one of the important tricyclicethylene moieties and recognized as an important drug candidate because of extensive applications in the field of medicinal and pharmaceutical chemistry. Recently, ample attention is given to this analogue by organic and medicinal chemistry community due to its successful utilization for the inhibition of estrogen receptor in MCF-7 breast cancer cell lines. Due to its structural character, tamoxifen is also useful in material chemistry. The synthesis of tamoxifen and its anlogues is desirable from easily available chemicals as an important drug candidate. Here, we report a review on various synthetic schemes for tamoxifen and its anlogues employing use of different strategies such as formation of CÀ C, C=C and C�C bonds, CÀ H functionalization, addition to alkynes, insertion reaction, nucleophilic substitution and addition reactions, elimination reaction, reductive couplings etc.

Stereoselective Access to Tetra‐ and Tri‐Substituted Fluoro‐ and Chloro‐Borylalkenes via Boron‐Wittig Reaction

“…In this case, the Z ‐isomeric product 13‐ Z was separable by standard silica gel chromatography. The resulting chloroalkene 13 ‐ Z was subjected to additional Pd‐catalyzed Suzuki–Miyaura cross‐coupling with 4‐cyanophenylboronic acid, affording the tamoxifen analogue 14 [29] with good E/Z ratio.…”

Remote-carbonyl-directed sequential Heck/isomerization/C(sp2)–H arylation of alkenes for modular synthesis of stereodefined tetrasubstituted olefins

“…All-carbon tetrasubstituted olefins extensively exist in natural products, leading drugs and functional organic materials 1 , 2 . They are also key precursors for various useful transformations such as hydrogenation, epoxidation, reductive Heck and other processes that generate contiguous highly substituted C(sp 3 ) centers 3 .…”

“…Here, we demonstrate that a remote-carbonyl-directed palladium-catalyzed Heck/isomerization/C(sp 2 )-H arylation sequence enables unactivated 1,1-disubstituted alkenes to undergo stereoselective terminal diarylation with aryl iodides, thus offering a concise approach to construct stereodefined tetrasubstituted olefins in generally good yields under mild conditions; diverse carbonyl groups are allowed to act as directing groups, and various aryl groups can be introduced at the desired position simply by changing aryl iodides. The stereocontrol of the protocol stems from the compatibility between the E/Z isomerization and the alkenyl C(sp 2 )-H arylation, where the vicinal groupdirected C(sp 2 )-H arylation of the Z-type intermediate product thermodynamically drives the reversible E to Z isomerization. Besides, the carbonyl group not only promotes the Pd-catalyzed sequential transformations of unactivated alkenes by weak coordination, but also avoids byproducts caused by other possible β-H elimination.…”

Pd/Cu Cooperative Catalysis for Heteroarylation of Vinyl C–H Bond Forming Polyaryl Ethylenes via C–O/Dual C–H Cleavage

“…Because of the unique chemical and physical properties, poly-substituted ethylenes have great applications in chemical, biological, and materials sciences . For example, polyaryl ethylenes exhibit a strong AIE (aggregation-induced emission) effect and can be used as a material for biological imaging, chemical sensing, and stimulus response. , They also commonly occur as the key units of some functional molecules such as natural products, drugs, and supra-molecules . Due to the transformation flexibility of double bonds, they can also be easily transformed into target compounds through addition, hydrogenation, oxidation, etc., thus acting as irreplaceable building blocks in organic synthesis …”