1. Generation of N-Heterocycles via Tandem Reactions of N '-(2-Alkynylbenzylidene)hydrazides
Guanyinsheng Qiu, Jie Wu Chem Rec. 2016 Feb;16(1):19-34. doi: 10.1002/tcr.201500219. Epub 2015 Oct 23.
As a powerful synthon, N '-(2-alkynylbenzylidene)hydrazides have been utilized efficiently for the construction of N-heterocycles. Since N '-(2-alkynylbenzylidene)hydrazides can easily undergo intramolecular 6-endo cyclization promoted by silver triflate or electrophiles, the resulting isoquinolinium-2-yl amides can proceed through subsequent transformations including [3 + 2] cycloaddition, nucleophilic addition, and [3 + 3] cycloaddition. Several unexpected rearrangements via radical processes were observed in some cases, which afforded nitrogen-containing heterocycles with molecular complexity. Reactive partners including internal alkynes, arynes, ketenimines, ketenes, allenoates, and activated alkenes reacted through [3 + 2] cycloaddition and subsequent aromatization, leading to diverse H-pyrazolo[5,1-a]isoquinolines with high efficiency. Nucleophilic addition to the in situ generated isoquinolinium-2-yl amide followed by aromatization also produced H-pyrazolo[5,1-a]isoquinoline derivatives when terminal alkynes, carbonyls, enamines, and activated methylene compounds were used as nucleophiles. Isoquinoline derivatives were obtained when indoles or phosphites were employed as nucleophiles in the reactions of N '-(2-alkynylbenzylidene)hydrazides. A tandem 6-endo cyclization and [3 + 3] cycloaddition of cyclopropane-1,1-dicarboxylates with N '-(2-alkynylbenzylidene)hydrazides was observed as well. Small libraries of these compounds were constructed. Biological evaluation suggested that some compounds showed promising activities for inhibition of CDC25B, TC-PTP, HCT-116, and PTP1B.
2. Natural hydrazine-containing compounds: Biosynthesis, isolation, biological activities and synthesis
Géraldine Le Goff, Jamal Ouazzani Bioorg Med Chem. 2014 Dec 1;22(23):6529-6544. doi: 10.1016/j.bmc.2014.10.011.
Hydrazine, hydrazone and hydrazide derivatives are nitrogen-nitrogen bond containing compounds. Such molecules are relatively scarce in nature and have been isolated from plants, marine organisms and microorganisms. These compounds exhibit remarkable structural diversity and relevant biological activities. The enzymes involved in the formation of the N-N bond are still unknown, but many lines of evidence support the involvement of N-nitrosation and N-hydroxylation activating steps. Beside the challenging N-N bond, N-acylases catalyzing the C-N bond formation contribute to the chemical diversity of N-N-containing natural products (N2NP). This review examines the state of knowledge regarding the biosynthesis of N2NP, for which only two biosynthetic gene clusters have been investigated. Biological properties and chemical synthesis of hydrazines, hydrazones and hydrazides are also reported.
3. Cyanoacetohydrazides in Synthesis of Heterocyclic Compounds
Hajar Hosseini, Mohammad Bayat Top Curr Chem (Cham). 2018 Oct 11;376(6):40. doi: 10.1007/s41061-018-0218-z.
Use of cyanoacetohydrazides as precursors in reactions leading to construction of heterocycles is reviewed. In addition to some common heterocyclic compounds, synthesis of other uncommon heterocycles such as thiadiazole, oxadiazole, fused heterocycles, and some seven- and eight-membered heterocycles such as benzodiazepine, oxazepine, and benzoxocine starting with cyanoacetohydrazides and their derivatives is also reported. The main aim of this review is to show the application of cyanoacetohydrazides in heterocyclic synthesis via different types of reaction, including cyclocondensation and cyclization. The results are arranged in terms of the type of heterocycle formed, from five-, six-, seven-, to eight-membered and fused rings. This review aims to cover literature up to 2018, showing the distribution of publications involving use of cyanoacetohydrazides for preparation of heterocycles.
