A Specialist Periodical Report Terpenoids and Steroids Volume 6 A Review of the Literature Published between September 1974 and August 1975 Senior Reporter K. H. Overton, Department of Chemistry, University of Glasgow Reporters D. V. Banthorpe, University College, London G. Britton, University of Liverpool B. V. Charlwood, King's College, London J. D. Connolly, University of Glasgow N. Darby, University of British Columbia, Vancouver, Canada J. R. Hanson, University of Sussex 0. N. Kirk, Westfield College, London T. Money, University of British Columbia, Vancouver, Canada P. J. Sykes, University of Edinburgh J. S. Whitehurst, University of Exeter R. B. Yeats, Bishop's University, Quebec, Canada @ Copyright 1976 The Chemical Society Burlington House, London, WIV OBN ISBN: 0 85186 306 X ISSN: 0300-5992 Library of Congress Catalog Card No. 74-615 720 Set in Times on Linotron and printed offset by J. W. Arrowsmith Ltd., Bristol, England Made in Great Britain Introduction Even a casual perusal of this volume will show that the health and vigour of terpenoid and steroid chemistry have in no way declined since the first Report in this series appeared in 1971. Nature continues to present us with the most unpredictable and challenging structures constructed from mevalonate. The toxic diterpenoids from Euphorbia species and the squalene-based Duphniphyllum alkaloids provide good recent examples. As X-ray analysis provides an almost routine procedure for unravelling even such complex structures, interest moves increasingly in the directions of biosynthesis and laboratory synthesis with a fruitful interplay in the area of biogenetically patterned synthesis. Characteristically, new instrumentation has been exploited and extended to the full, the outstanding example being 13C n.m.r. spectroscopy and particularly its use as a non-destructive method for establishing labelling patterns in biosynthesis. Resourcefulness and ingenuity abound in meeting aesthetic and commercial challenges in the field of synthesis. As I hand over the task of Senior Reporter to my successor, Dr. J. R. Hanson, it is a pleasure to record my gratitude to all the colleagues who have written these Reports for their enthusiastic and unstinting collaboration. K. H. OVERTON Cont en ts Part I Terpenoids Chapter 1 Monoterpenoids 3 By R. B. Yeats 1 Physical Measurements: Spectra efc.; Chirality 3 2 General Synthetic Reactions 6 3 Biogenesis, Occurrence, and Biological Activity 10 4 Acyclic Monoterpenoids 14 Terpenoid Synthesis from Isoprene 14 2,6-Dimethyloctanes 15 Halogenated Monoterpenoids 19 Artemisyl, Santolinyl, Lavandulyl, and Chrysanthernyl Derivatives 20 5 Monocyclic Monoterpenoids 21 Cyclobutane 21 Cyclopentanes, Iridoids 23 pMent hanes 27 o-Menthanes 31 rn-Menthanes 32 Tetramethylcyclohexanes 32 Dimet hylethylcyclohexanes 33 Cycloh ep tanes 33 6 Bicyclic Monoterpenoids 35 Bicyclo[3,1, O]hexanes 35 Bicycle[ 2,2 ,1 1 heptanes 35 Bicyclo[3,l,l]heptanes 41 Bicyclo[4,170]heptanes 45 7 Furanoid and Pyranoid Monoterpenoids 47 8 Cannabinoida and other Phenolic Monoterpenoids 48 V vi Terpenoids and Steroids Chapter 2 Sesquiterpenoids 52 By N. Darbyand T. Money 1 Farnesanes 52 2 Bisabolanes 56 3 Sesquicarane 59 4 Sesquipinane (Bergamotane), Sesquifenchane, Sesquicamphane, Santalane 60 5 Acorane, Carotane, Cedrane 61 6 Cuparane, Laurane, Trichothecane, Cyclotrichothecane 62 7 Chamigrane efc. 64 8 Amorphane, Cadinane, Copacamphane, Sativane, efc. 65 9 Himachalane, Longipinane, Longicamphane, Longifolane, 69 efc. 10 Humulane, Caryophyllane, Hirsutane, Protoilludane, Illudane, Marasmane 71 11 Germacrane, Eudesmane, Vetispirane 75 12 Guaiane, Aromadendrane, Pseudoguaiane 88 13 Mono- and Bi-cyclofarnesanes 91 14 Miscellaneous 94 Chapter 3 Diterpenoids 96 ByJ. R. Hanson 1 Introduction 96 2 Bicyclic Diterpenoids 97 Labdanes 97 Clerodanes 99 3 Tricyclic Diterpenoids 100 Naturally Occurring Substances 100 The Chemistry of the Tricyclic Diterpenoids 102 4 Tetracyclic Diterpenoids 105 The Kaurene-Phyllocladene Series 105 Be yeranes 107 Gibberellins 109 Diterpenoid Alkaloids 111 Contents vii 5 Macrocyclic Diterpenoids and their Cyclization Products 112 115 6 Miscellaneous Diterpenoids 7 Diterpenoid Synthesis 116 118 Chapter 4 Triterpenoids By J. D. Connolly 118 1 Squalene Group 2 Fusidane-Lanostane Group 120 3 Darnmarane-Euphane Group 123 Tetranortriterpenoids 126 Quassinoids 128 4 Shionane Group 129 5 LupaneGroup 130 6 Oleanane Group 132 7 UrsaneGroup 139 8 HopaneGroup 140 9 Serratane Group 141 144 Chapter 5 Carotenoids and Polyterpenoids By G. Britton 1 Introduction 144 2 Carotenoids 144 New Natural Carotenoids 144 New Degraded Carotenoids 147 Stereochemistry 148 Carotenoids 148 Degraded Carotenoids 149 Synthesis and Reactions 149 Carotenoids 149 Retinal Derivatives 153 Other Degraded Carotenoids 155 ... Vlll Terpenoids and Steroids Physical Methods and Physical Chemistry 162 Separation and Assay Methods 162 Mass Spectrometry 163 'H N.M.R. Spectroscopy 163 13CN .M.R. Spectroscopy 163 X-Ray Crystallography 164 Electronic Absorption Spectroscopy 164 Retinal as Visual Pigment Model: Spectroscopy and Physical Chemistry 165 Miscellaneous Physical Chemistry 165 3 Polyterpenoids and Quinones 165 Polyterpenoids 165 Quinones 166 Chapter 6 Biosynthesis of Terpenoids and Steroids 169 By D. V. Banthorpe and B. V. Charlwood 1 Introduction 169 2 Acyclic Precursors 170 3 Hemiterpenoids 177 4 Monoterpenoids 177 5 Sesquiterpenoids 180 6 Diterpenoids 187 7 Sesterterpenoids 190 8 Steroidal Triterpenoids 190 9 Further Metabolism of Steroids 200 10 Non-steroidal Triterpenoids 208 11 Carotenoids 209 12 Polyterpenoids 21 1 13 Meroterpenoids 211 14 Methods 215 15 Chemotaxonomy 217