Total synthesis

About: Total synthesis is a research topic. Over the lifetime, 25578 publications have been published within this topic receiving 489319 citations.

Synthesis of Medium-Sized Ring Lactams

Abstract: Medium-sized ring lactams (7- to 15-membered) find widespread use in organic chemistry as key intermediates in the synthesis of more complex structures or as core structures in natural product or pharmaceutically important compounds. Until now, the generation of such rings is still a challenge in organic synthesis. During the past decade an increasing interest has focused on the generation of cyclic peptides as well as hairpin and β-turn mimics and the medium-sized rings were thought to represent suitable fragments. Furthermore, a range of complex natural products is characterized by such lactam structure and their total synthesis is a broad field for organic chemists to test new strategies and to develop new methods.

Total Synthesis of (±)- and (−)-Actinophyllic Acid

Abstract: Development of efficient sequences for the total syntheses of (±)-actinophyllic acid (rac-1) and (−)-actinophyllic acid (1) are described. The central step in these syntheses is the aza-Cope/Mannich reaction, which constructs the previously unknown hexacyclic ring system of actinophyllic acid in one step from much simpler tetracyclic precursors. The tetracyclic hexahydro-1,5-methano-1H-azocino[4,3-b]indole ketone rac-37 is assembled from o-nitrophenylacetic acid in four steps, with oxidative cyclization of a dienolate derivative of tricyclic precursor rac-35 being the central step. In the first-generation synthesis, this intermediate is transformed in two steps to homoallyl amine rac-43, whose formaldiminium derivative undergoes efficient aza-Cope/Mannich reaction to give pentacyclic ketone rac-44. In four additional steps, this intermediate is advanced to (±)-actinophyllic acid. The synthesis is streamlined by elaborating ketone rac-37 to β-hydroxyester intermediate rac-53, which is directly transformed ...

Total synthesis of (+)-isatisine A.

Abstract: The asymmetric total synthesis of (+)-isatisine A has been accomplished commencing with a Lewis acid-catalyzed cyclization of homochiral (S)-vinylcyclopropane diester and N-tosylindole-2-carboxaldehyde to construct the tetrahydrofuran ring. A palladium-catalyzed oxidative decarboxylation was utilized to obtain the dihydrofuran required for the subsequent dihydroxylation reaction to install the diol present on the tetrahydrofuran ring. The total synthesis was completed by an indole oxidation and electrophilic aromatic substitution sequence to construct isatisine A acetonide, which was then carried forward to the antipode of the natural product. The absolute configuration of the natural enantiomer (-)-isatisine A was determined to be C2(S), C9(R), C10(S), C12(R), and C13(R).

Role of the Nozaki–Hiyama–Takai–Kishi Reaction in the Synthesis of Natural Products

Abstract: The Nozaki–Hiyama–Takai–Kishi (NHTK) reaction was discovered in the late 1970s and, since then, its main application has been its use in total synthesis. In this comprehensive review, the efficiency of the NHKT reaction in the synthesis of a great number of different scaffolds present in complex natural products is analyzed. The preparation of enol and allylic and propargylic alcohol motifs is discussed, highlighting factors such as yield, chemoselectivity, stereoselectivity, or the importance of protecting groups. The review is divided into two main sections: intermolecular and intramolecular NHTK reactions. A final discussion about the current “state-of-art” and future perspectives for the use of this transformation in total synthesis is also included.