Natural and Synthetic Spirobutenolides and Spirobutyrolactones

Abstract

Spirobutenolides and spirobutyrolactones structural motifs are widespread in various natural products that exhibit a broad array of biological activities. Additionally, their synthetic analogues also serve as biologically active compounds and building blocks of complex molecules. Owing to the wide range of pharmacological activities and structural diversity of the spirobutenolides and spirobutyrolactones, various efficient synthetic methodologies have been established to construct such interesting scaffolds. In the past decades, numerous total syntheses of spirobutenolides and spirobutyrolactones containing natural products have been reported. Structurally diverse spirobutenolides and spirobutyrolactones have been synthesized by using singlet oxygen, Mannich reaction, aldol condensation, rearrangement reaction , Reformatsky reaction, Michael-addition cyclization, Diels-Alder reaction, photocyclization reaction, and pericyclic reactions. Recently, metal-catalyzed cyclization, photocatalyzed radical cyclization, Baylis-Hillman reaction, asymmetric organocatalysis, NHC catalysis, ring contraction reactions, and hypervalent iodine catalysis have emerged as powerful tools to architect these nuclei. This review gives an overview of advancements in chemically and biologically relevant spirobutenolides and spirobutyrolactones of natural and synthetic origin. It also covers the newer methodologies for the construction of natural as well as synthetic spirobutenolides and spirobutyrolactones along with their potential applications.

Spiro Derivatives in the Discovery of New Pesticides: A Research Review

“…Despite these characteristics, there are few studies on these structures in pesticides, and most of them focus on their pharmaceutical activities. 76 Spirodinaphthalene derivatives have broad spectrum insecticidal, bactericidal, and fungicidal properties. For example, compounds 46 (Palmarumycin C8) and 45 (Palmarumycin B6) had significant insecticidal effects against Aedes albopictus with LC 50 values of 8.83 and 11.51 mg/L, respectively.…”

“…According to the literature summary, the introduction of active spirocyclic structures into neonicotinoid compounds, indole compounds, and natural products improves their insecticidal activities against Lepidoptera , Hemiptera , and Diptera insects and other pests. − Neonicotinoids are currently the most widely used insecticides. They act on nicotinic acetylcholine receptors in the insect’s nervous system and peripheral nerves, causing paralysis. , These compounds are highly efficient and selective broad spectrum insecticides.…”

“…The asymmetric total synthesis of (+)-croomine , therefore, provides the possibility for novel discoveries of insecticidal molecules via a synthetic routine. Despite these characteristics, there are few studies on these structures in pesticides, and most of them focus on their pharmaceutical activities . Spirodinaphthalene derivatives have broad spectrum insecticidal, bactericidal, and fungicidal properties.…”

Natural‐Like Spirocyclic Δα,β‐Butenolides Obtained from Diazo Homophthalimides

“…Thus, spirocycles simultaneously address two important trends in modern drug design: the tendency to design more ‘three‐dimensional’ scaffolds [5–6] and the higher preference towards molecules possessing more sp 3 ‐hybridized atoms (higher‐F sp3 compounds) [7–8] . Perhaps it is unsurprising that the special position and prominence of Δ α,β ‐spirobutenolides in the bioactive compound domain [3] has driven the development of the relevant synthetic methodology [3a,9] …”

Direct synthesis of fluorene-based spirolactones through a BF3-promoted spiroannulation of α-keto acids and o-alkynylbiaryls

“…Spirolactones, an important class of heterocycles, are privileged frameworks that are widely featured in biologically active natural chemicals and pharmaceutical molecules, 7 and they play increasingly significant roles in the field of medical science because of their distinct biological and pharmaceutical activities, including anti-inflammatory, antibiotic, and antitumor activities. Thus, many synthesis procedures, such as the Dieckmann condensation, 8 Diels–Alder cycloaddition, 9 and transition metal-catalyzed tandem cyclization reactions, 10 have been developed to build spirolactone derivatives.…”