Review On the origins of triterpenoid skeletal diversity Ran Xu, Gia C. Fazio, Seiichi P.T. Matsuda* Department of Chemistry and Department of Biochemistry and Cell Biology, Rice University, 6100 S. Main Street, Houston, TX 77005, USA Received 22 July 2003; received in revised form 31 October 2003 Dedicated to Prof. E. J. Corey on the happy occasion of his 75th birthday Abstract The triterpenoids are a large group of natural products derived from C 30 precursors. Nearly 200 different triterpene skeletons are known from natural sources or enzymatic reactions that are structurally consistent with being cyclization products of squalene, oxidosqualene, or bis-oxidosqualene. This review categorizes each of these structures and provides mechanisms for their formation. # 2003 Elsevier Ltd. All rights reserved. Keywords: Triterpene; Triterpenoid; Oxidosqualene cyclization; Squalene; Cyclization; Isoprene rule 0031-9422/$ - see front matter # 2003 Elsevier Ltd. All rights reserved. doi:10.1016/j.phytochem.2003.11.014 Phytochemistry 65 (2004) 261–291 www.elsevier.com/locate/phytochem Contents 1. Introduction ............................................................................................................................................................................... 262 2. Oxidosqualene cyclization .......................................................................................................................................................... 263 2.1. Monocyclic triterpene alcohols .......................................................................................................................................... 264 2.2. Bicyclic triterpene alcohols ................................................................................................................................................ 264 2.3. Tricyclic triterpene alcohols............................................................................................................................................... 265 2.4. Tetracyclic triterpene alcohols ........................................................................................................................................... 265 2.4.1. Tetracyclic 6-6-6-5 triterpene alcohols derived from the protosteryl cation: protostane, lanostane, cucurbitane, and related skeletal types....................................................................................................................................... 265 2.4.2. Tetracyclic 6-6-6-5 triterpene alcohols derived from the dammarenyl cation: dammarane, euphane, tirucalane, and related skeletal types....................................................................................................................................... 267 2.4.3. 6-6-6-6 Triterpene alcohols derived from the dammarenyl cation: baccharane and related skeletal types............ 267 2.5. Pentacyclic triterpene alcohols........................................................................................................................................... 267 2.5.1. Pentacyclic C–B–C–C(–C) 6-6-6-6-5 or 6-6-6-6-6 rings: arborinane, stictane, and related skeletal types ............. 267 2.5.2. Pentacyclic C–C–C–C(–C) 6-6-6-6-5 or 6-6-6-6-6 rings: lupane, germanicane, taraxastane, ursane, and other skeletal types, D-ring expansion via C16 migration followed by 18b E-ring cyclization and possible E-ring expansion............................................................................................................................................................... 268 2.5.3. Pentacyclic C–C–C–B(–C) 6-6-6-6-5 or 6-6-6-6-6 rings, D-ring expansion via C16 migration followed by 18a E-ring cyclization and possible E-ring expansion .................................................................................................. 271 2.5.4. Pentacyclic C–C–C–C 6-6-6-6-5 rings via a spiro-fused 5,5 D–E ring intermediate .............................................. 272 2.6. Pentacyclic C–C–C–C(–C) 6-6-6-6-5 or 6-6-6-6-6 rings: 3-hydroxyhopane, moretane, tetrahymane, and other skeletal types that are structurally consistent with direct cyclization ............................................................................................. 273 3. Squalene cyclization ................................................................................................................................................................... 274 3.1. Monocyclic triterpenes and their derivatives that originate from squalene (Fig. 21) ........................................................ 275 3.2. Bicyclic triterpenes and their derivatives that originate from squalene (Fig. 22) .............................................................. 275 3.3. Tricyclic triterpenes derived from squalene cyclization (Fig. 23) ...................................................................................... 276 * Corresponding author. Tel.: +1-713-348-6158; fax: +1-713-348-5154. E-mail address: matsuda@rice.edu (S.P.T. Matsuda).