Spiro-Flavonoids in Nature: A Critical Review of Structural Diversity and Bioactivity

Abstract

Based on the literature data from 1973 to 2022, this work summarizes reports on spiro-flavonoids with a spiro-carbon at the center of their structure and how this affects their isolation methods, stereochemistry, and biological activity. The review collects 65 unique structures, including spiro-biflavonoids, spiro-triflavonoids, spiro-tetraflavonoids, spiro-flavostilbenoids, and scillascillin-type homoisoflavonoids. Scillascillin-type homoisoflavonoids comprise spiro[bicyclo[4.2.0]octane-7,3′-chromane]-1(6),2,4-trien-4′-one, while the other spiro-flavonoids contain either 2H,2′H-3,3′-spirobi[benzofuran]-2-one or 2′H,3H-2,3′-spirobi[benzofuran]-3-one in the core of their structures. Spiro-flavonoids have been described in more than 40 species of eight families, including Asparagaceae, Cistaceae, Cupressaceae, Fabaceae, Pentaphylacaceae, Pinaceae, Thymelaeaceae, and Vitaceae. The possible biosynthetic pathways for each group of spiro-flavonoids are summarized in detail. Anti-inflammatory and anticancer activities are the most important biological activities of spiro-flavonoids, both in vitro and in vivo. Our work identifies the most promising natural sources, the existing challenges in assigning the stereochemistry of these compounds, and future research perspectives.

Annulations involving p-benzoquinones: stereoselective synthesis of fused, spiro and bridged molecules

“…Spirocycles are ubiquitous in natural products, synthetic drugs and functional materials. 89 Because of their attractive biological profile, the stereoselective synthesis of spiro compounds has long been pursued by chemists. 90 The synthesis of chiral multi-substituted 3H-spiro[benzofuran-2,1 0 -cyclopentane] 89 from readily accessible benzoquinones 86 and allylic alcohols 87 was reported by Wang et al 91 The catalysis system Cu(II)/BOX was found to be suitable to generate intermediate 88, which upon treatment with Lewis acid SnCl 4 provided final spiro products 89.…”

“…Spirocycles are ubiquitous in natural products, synthetic drugs and functional materials. 89 Because of their attractive biological profile, the stereoselective synthesis of spiro compounds has long been pursued by chemists. 90…”

Synthesis and Analytical Characterization of Cyclization Products of 3-Propargyloxy-5-benzyloxy-benzoic Acid Methyl Ester

“…Chromane is a bicyclic scaffold, ubiquitous in a wide variety of bioactive natural products and synthetic compounds exhibiting antitumor, anti-inflammatory, antiviral, antiprotozoal, and antimicrobial effects [1][2][3][4][5][6][7][8][9][10]. Among them, some have also shown moderate-to-good antitubercular activities [11][12][13][14][15][16][17][18].…”