Total Synthesis OfNatural Products, Volume1 Edited by John Apsimon Copyright © 1973 by John Wiley & Sons, Inc THE TOTAL SYNTHESIS OF NATURAL PRODUCTS Total Synthesis OfNatural Products, Volume1 Edited by John Apsimon Copyright © 1973 by John Wiley & Sons, Inc The Total Synthesis of Natural Products VOLUME Edited by JOHN ApSimon Department of Chemistry Carleton tmiuersify, Ottawa WILEY-INTERSCIENCE, a Division of John Wley & Sons, Inc New York -.London Sydney Toronto A NOTE TO THE READER This book has been electronically reproduced from digital information stored at John Wileydr Sons, Inc We are pleased that the use of this new technology will enable us to keep works of enduring scholarly value in print as long as there is a reasonable demand for them The content of this book is identical to previous printings Copyright @ 1973 , by John Wiley & Sons, Inc All rights reserved Published simultaneously in Canada Reproduction or translation o f any part of this work beyond that permitted by Sections 107 or 108 o f the 1976 United States Copyright Act without the permission of the copyright owner is unlawful Requests for periiii~nionor further information should be addressed to thc Permissions Departnient John Wiley & Sons Inc Library of Congress Cataloging in Publication Data: ApSimon, John The total synthesis of natural products Includes bibliographical references Chemistry, Organic-Synthesis Title QD262.A68 547l.2 ISBN 0-471-03251-4 12-4075 Printed in the United States of America I0 Contributors to Volume U F A F J Axen, Upjohn Company, Kalamazoo, Michigan M Dean, University of Liverpool, England H Jackson, University College, Cardiff, United Kingdom Johnson, Dow Chemical Company, Wayland, Massachusetts K N Jones, Queen’s University, Kingston, Ontario S A Narang, National Research Council of Canada, Ottawa J E Pike, Upjohn Company, Kalamazoo, Michigan W P Schneider, Upjohn Company, Kalamazoo, Michigan K M Smith, University of Liverpool, England W A Szarek, Queen’s University, Kingston, Ontario R H Wightman, Carleton University, Ottawa, Ontario Preface Throughout the history of organic chemistry we find that the study of natural products frequently has provided the impetus for great advances This is certainly true in total synthesis, where the desire to construct intricate and complex molecules has led to the demonstration of the organic chemist’s utmost ingenuity in the design of routes usingestablished reactions or in the production of new methods in order to achieve a specific transformation These volumes draw together the reported total syntheses of various groups of natural products with commentary on the strategy involved with particular emphasis on any stereochemical control No such compilation exists at present and we hope that these books will act as a definitive source book of the successful synthetic approaches reported to date As such it will find use not only with the synthetic organic chemist but also perhaps with the organic chemist in general and the biochemist in his specific area of interest One of the most promising areas for the future development of organic chemistry is synthesis The lessons learned from the synthetic challenges presented by various natural products can serve as a basis for this everdeveloping area It is hoped that this series will act as an inspiration for future challenges and outline the development of thought and concept in the area of organic synthesis The project started modestly with an experiment in literature searching by a group of graduate students about six years ago Each student prepared a summary in equation form of the reported total syntheses of various groups of natural products It was my intention to collate this material and possibly publish it During a sabbatical leave in Strasbourg in the year 1968-1969, I attempted to prepare a manuscript, but it soon became apparent that if was to also enjoy other benefits of a sabbatical leave, the task would take many years Several colleagues suggested that the value of such a collection vii viii Preface would be enhanced by commentary The only way to encompass the amount of data collected and the inclusion of some words was to persuade experts in the various areas to contribute I am grateful to all the authors for their efforts in producing stimulating and definitive accounts of the total syntheses described to date in their particular areas I would like to thank those students who enthusiastically accepted my suggestion several years ago and produced valuable collections of reported syntheses They are Dr Bill Court, Dr Ferial Haque, Dr Norman Hunter, Dr Russ King, Dr Jack Rosenfeld, Dr Bill Wilson, Mr Douglas Heggart, Mr.George Holland, and Mr Don Todd I also thank Professor Guy Ourisson for his hospitality during the seminal phases of this venture JOHN APSIMON Ottawa, Canada Febrrtary 1972 Contents The Total Synthesis of Carbohydrates J K N JONESand W A SZAREK The Total Synthesis of Prostaglandins u AXBN,J E PIKE, AND w P SCHNEIDER The Total Synthesis of Pyrrole Pigments 81 143 A H JACKSON AND K H SMITH The Total Synthesis of Nucleic Acids s A NARANG AND R H 279 WIGHTMAN The Total Synthesis of Antibiotics 331 F JOHNSON The Total Synthesis of Naturally Occurring Oxygen Ring Compounds 467 F M DEAN Subject Index 563 Reaction Index 597 ix THE TOTAL SYNTHESIS OF NATURAL PRODUCTS Total Synthesis OfNatural Products, Volume1 Edited by John Apsimon Copyright © 1973 by John Wiley & Sons, Inc The Total Synthesis of Carbohydrates J K N JONES AND W.A SZAREK Department of Chemistry, Queen's University, Kingston, Ontario, Canada Introduction Base-Catalyzed Condensations with Carbon-Carbon Bond Formation The Formose Reaction Syntheses from Acetylenic and Olefinic Precursors Syntheses from Tartaric Acid and Other Naturally Occurring Acids The Diels-Alder Reaction Syntheses from Furan and Pyran Derivatives Miscellaneous Syntheses A Amino Sugar Derivatives B Deoxyfluoro Sugar Derivatives C Branched-Chain Sugars Enzymic Syntheses Synthesis of Cyclitols References 19 24 28 58 58 60 62 64 66 75 INTRODUCTION The carbohydrates comprise one of the major classes of naturally occurring organic compounds Although the structures of carbohydrates appear to be quite complex, the chemistry of these compounds usually involves only two kinds of functional group, ketone or aldehyde carbonyls and hydroxyl groups The carbonyl groups normally are not free but are combined with The Total Synthesis of Carbohydrates the hydroxyl groups in hemiacetal or acetal linkages; the carbon of the “masked” carbonyl is known as the anomeric center When a free sugar is dissolved in an appropriate solvent, a dynamic equilibrium is achieved involving both anomerization and ring isomerization A wide variety of sugars has been found in nature and/or synthesized in the laboratory These include not only the “classical” sugars but also derivatives such as amino, thio, halo, deoxy , branched-chain, and unsaturated sugars Most synthetic sugars have been obtained by chemical transformations of naturally occurring sugars or their derivatives In fact, the degree of achievement is such that the synthesis of a new mono-, di-, or trisaccharide can now be undertaken with a fair degree of confidence The total synthesis of sugars from noncarbohydrate precursors has also been achieved by many routes Some methods are long, involved, are stereospecific and result in the formation of one or two sugars only; others are relatively simple but produce complex mixtures of carbohydrates which may resist fractionation Practically all naturally occurring sugars are optically active Most synthetic routes which employ noncarbohydrate precursors produce racemic mixtures of sugars which may be difficult to separate into the D and L isomers However, if enzymes are used to effect condensation of fragments or to remove one or more of the components, optically pure isomers may be isolated In this chapter the total synthesis of sugars and the related alditols and cyclitols, from noncarbohydrate substances by both specific and nonspecific methods, are discussed Only compounds containing more than three carbon atoms are considered BASE-CATALYZED CONDENSATIONS WITH CARBON-CARBON BOND FORMATION THE FORMOSE REACTION The formose reaction has attracted the attention of biologists and chemists in recent years because it involves the self-condensation of formaldehyde to produce reducing sugars This property is of interest in considering the problem of the origin of life on this planet, especially as formaldehyde has been detected in interstellar gases,‘ and also because of the feasibility of using carbon (as formaldehyde) as a possible source of sugars for the growth of microorganisms with the concomitant production of proteins and other complex organic compounds of importance to life and industry.2 The self-condensation of formaldehyde under the influence of base to yield a sugarlike syrup (methylenitan) was first observed by ButlerowS in 1861, when he treated trioxymethylene with calcium hydroxide solution Calcium carbonate, magnesia, baryta, mineral clay, or even y-radiation 588 Subject Index amines, 359 as protecting group for amines, 409-426 Phytoalexins, 516, 524, 525 Pinacol rearrangement, of dihydroxychlorins, 201 Piperidine, in cleavage of anisoles, 551 as condensing agent, 495, 505 Pipcridones, 254 condensation with 1,3-diketones, 254 imino ether formation, 251 see also Amides; Lactams Pivaloyl esters, as protecting group for alcohols, 288 Plexaura homomalla, prostaglandin extraction, 84, 119 Polyenones, from 1,3-diones, 120 Polymerisation, in synthesis of oligonucleotides, 293-299 Polymer supports, in synthesis of oligonucleotides, 309-31 Polymixins, 404, 413419 Polynucleotide kinase, in enzymic synthesis of oligonucleotides, 319 Polynucleotide ligase, in enzymic synthesis of oligonucleotides, 320-321 Polynucleotidyl phosphorylase, in enzymic synthesis of oligonucleotides, 317318 Polyphosphoric acid, as condensing agent, 500, 510, 526, 535-539 as dehydrating agent, 355 Porphobilinogen, incorporation of 6aminolevulinic acid, 156 Porphyrinogens, 187, 199-209 oxidation, 199-209 Porphyrins, acetylation, 173 formylation, 182 Friedel-Crafts reaction, 173, 182 hydrogenation, 202 metabolism, 193, 194 oxidation, 210,211 reduction, 199-209 synthesis from a,c-biladienes, 179-184 b-bilenes, 194-199 a-oxobilanes, 184-187 6-oxobilanes and oxophlorins, 187-194 pyrroketones, 176-179 pyrroles, 166-167 pyrromethanes, 167-169 pyrromethenes, 169-176 Potassium carbonate, as condensing agent, 14 Potassium ferricyanide, in oxidative couplings, 422,441 Potassium iodate, as oxidising agent, 516521 Potassium permanganate, in oxidative denitration of nitroalkanes, 385 Prdvost reagent, 68 Pristinamycins, 404 Prodigiosin, 227-232 Prostaglandins, 81-138 biosynthesis and metabolism, 84-89 Prostanoic acid, 82 Pterocarpins, 512-525 Purine Nucleosides, 390-398 Purpurins, 202 oxidative cleavage of isocyclic ring, 202 Pyranocoumarins, 484 Pyran-4-oncs, see Xanthones; lsoflavones Pyranoxanthones, 548-555 Pyrans, as carbohydrate precursors, 28-58 conformational analysis, 28-58 Pyridine, as condensing agent, 552 Pyridinium chloride, as condensing agent, 542 Pyridinium hydrobromide perbromide, as halogenating agent, 231 5’-Pyridinium methylpyrroketones, coupling with pyrromethane-5-carboxylic acids, 185 Pyridones, hydrogenation, 158; see also Amides; Lactams Pyrones, condensation with carbanionic reactants, 526 Pyronoquinones, see Amphipyrones Pyrroketones, 164-165 abnormal keto function, 164 modified nucleophilicity, 177, 185 reduction, 164 in synthesis of porphyrins, 176-179 Pyrrole, polymerisation with aldehydes, 150 Pyrrole carboxylic acids, decarboxylation, 157,159,217,220,222,226,230 iodinative decarboxylation, 157, 159 Pyrrole Grignard reagents, 162 condensation with acyloxymethylpyrroles, 162 alkoxymethylpyrroles, 162 chlorocarbonylpyrroles, 162 Subject Index halomethylpyrroles, 162 self-condensation, 199 Pyrroles, addition with A'-pyrrolines, 230 condensation with acyloxymethylpyrroles, 162 alkoxymethylpyrroles, 162 bromomethylpyrrolinones, 14 5,5'-diformylpyrromethanes, 183 dimethylamidopyrrole/POCI,complex, 165 ethyl orthoformate, 219, 222, 226 formaldehyde, 161 formylpyrroles, 143-271 halomethylpyrroles, 162 halomethylpyrrolinones, 14 phosgene, 165 pyrrolidones, 230 2-pyrrodinones, 230 formylation with HCN,219, 223 Gatterman reaction, 219 oxidation, 214 reductive C-alkylation, 154-155 synthesis by, formation of C-N bonds, 150,232 3-4 and C-N bonds, 150-152 2-3 and C-N bonds, 152-153 2-3 and 4-5 bonds, 153-154 from other heterocycles, 154 in synthesis of porphyrins, 166-167 Vilsmeier condensation, 230 Pyrrolidones, 217,219,221, 235,239,246 condensation with pyrroles, 230 a$-unsaturated nitriles, 243 imino ether formation, 249 thiolactam formation, 241, 249 Vilsmeier reaction, 230 see also Amides; Lactams Pyrrolines, addition of iodine azide, 456 synthesis from isoxazoles, 26 1-268 A'-Pyrrolines, addition with pyrroles, 230 Pyrrolinones, 214,219,227 as carbanionic reactants, 219 condensation with formylpyrroles, 219, 220,225 hydrogenation, 221 reduction, 219 Vilsmeier condensation, 230 see also Amides; Lactams Pyrrolinylpyrroles, 230 dehydrogenation, 230 589 Pyrrolo( 1,2-a)indoles, 455457 carbomethoxylation, 456 Pyrrolopyrimidine Nucleosides, 398400 N-substitution, 400 Pyrrolylmethylenepyrrolinones,2 17 condensation with formylpyrrolylmethy Ienepyrrolinones, 217 formylation, 217 reduction, 219 Pyrrolylmethylpyrrolinones,2 15 condensation with formylpyrrolylmethylpyrrolinones, 217 dehydrogenation, 217 formylation, 217 hydrogenation, 217, 219 oxidation, 217 Pyrromethane amides, complex formation with POCI,, 187,189, 191 condensation with pyrromethanes, 187, 189, 191 Pyrromethane-a-carbox ylic acids, condensation with a-formylpyrromethanes, 195, 197 5'-pyridiniummethylpyrroketones, 185 Pyrromethanes, 161-163,213 acid-catalysed isomerisation, 167 condensation with 5,5'-di(bromomethyl)pyrromethene, 169 5,5'-diformylpyrroketones, 177 5,5'-diform ylpyrromethanes, 168 formic acid, 167 a-formylpyrromethanes, 195, 214 pyrromethane amides, 187, 189, 191 oxidation, 165,213, 215 in synthesis of porphyrins, 166-167 Pyrromethenes, 163-164,214 condensation with formylpyrromethanes, 214,215 Friedel-Crafts reaction, 180 reduction, 225 in synthesis of porphyrins, 169-176 N-Pyruvylideneglycinatoaquocopper(ll), in Akabori reaction, 60 Quercitols, 66-75 Quinone methides, 471485 cyclisation, 471-485 reduction, 476479 Quinones, addition with dihydrofurans, 487 vinyl ethers, 487 590 Subject Index benzylation, 487 condensation with chromanones, 12 coupling with hydroxycoumarins, 16521 coupling with phenols, 516-521 Diels-Alder reaction, 356, 360 as intramolecular oxidising agents, 476 methylation, 487 reduction, 356 ?Radiation, as condensing agent, Radicicol, 427 Reduction, of acetylenes, 13, 14 of acetylenic ethers, 471-472 of acid chlorides, 21, 58 of acylazides under mild conditions, 458 of alcohols, 378 of aldehydes, 1, 43 of alkyl halides, 108, 112 with aluminium amalgam, 97, 100, 101, 34 of aryl ethers, 115, 251,265 of aryl ketones, 476-479, 533 of azides, 235, 343,376,378,403,456 of bilirubin, 213 Birch reduction, 115 with borohydride, 178,476-479, 501, 502,504,509,523,524 of carboxylic acids, 4, 18 of chlorins 209 of chromanones, 476,533 of chromenes, 472 of chromenochromones, 501-502 with chromous acetate, 118 of coumarins, 490, 522 of cyclobutylketones, 125 of 2,4-diacetyloxophlorins, 178 with diborane, 43, 164, 522, 533 with di-i-butyl aluminium hydride, 109, 113 of dienediones selectively, 13 with disiamylborane 18, 491, 495 electrolytic, 209 of epoxides, 36.45.46 of a,p-epoxy ketones, 118 of esters, 230 under mild conditions, 458 of a-haloketones, 113, 125 of hemiacetal lactones, 491,495 by hindered hydride reagents, 18, 20, 108, 109,113, 115,439,491.495 of hydrazides under mild conditions, 458 of isoflavones, 523, 524 of isoxazoles, 261-268 of ketodienol ethers, 120 of a-ketodiesters, 268 of 0-ketoesters, 265 of lactones, 23,47,51,64,92, 109, 351, 377,488,491,495,522,533 in the presence of epoxides, 113 with lithium aluminium hydride, 13, 14, 23, 36,4547, 51,54, 56,64 with lithium tri-t-butoxyaluminium hydride, 20, 115 McFadyen-Stevens reduction, 230 of nitriles, 232 of nitroalkanes, 97, 100, 101, 359, 382 of nitrobenzenes, 438 of nitrosugars, 369 of oximes, 368, 382, 384 of oximinones, 150 of a-oxobilanes, 185 of polycarbonyl compounds, 351,491, 495 of polyesters, 133 of porphyrins, 199-209 of pyrroketones, 164 of pyrrolinones, 219 of pyrromethenes, 225 of pyrrolylmethylenepyrrolinones,219 of quinone methides 476-479 of quinones, 356 Rosenmund reduction, 21,58 with sodium amalgam, 4.21, 368 with sodium borohydride, effect of silylation, 118 with sodium dithionite, 345,403,438 of sulphoxides, 345 in synthesis of cis-fused rings, 502, 504, 509 of L-tartaric acid, 20 of tosylates, 54 with tri-r-butyl stannous hydride, 108 of a$-unsaturated ketones, 56, 501-504, 509 of vinyl bromides, 550 of vinyl ethers, 501 502.504, 509 see also Hydrogenation; Hydrogenolysis; Reductive cleavage; and Reductive Dimerisation Subject Index cis-Reduction, with di-imide in pyridine, 199 of olefins, 199 trans-Reduction, of olefins, 199 with sodium in alcohol, 199 Reductive C-alkylation, of pyrroles, 154155 Reductive cleavage, of aryl ethers, 441 of aJ-epoxyketones, 118 with sodium in liquid ammonia, 235 of 1,1,2,2-tetracarboxylic esters, 235 of thioethers, 393 of tosylates, 378 see also Hydrogenation; Hydrogenolysis; Reduction Reductive dimerisation, of acrolein, Reductive methylation, of amines, 381 with HCHOIH, /Pd, 381 Reformatsky reaction, of aldehydes, 18 of a-haloesters, 18 of a,p-unsaturated aldehydes, 18 Resolution of optical isomers, 4, 7,9, 17, 53,99, 108, 129, 135, 138,202, 222,226,245,262,265, 267, 338, 425,441,444,458,503-504,532 Resorcinols, 467-555 acetoxylation, 527-528,530, 532 aldimine formation, 527 alkylation, 528-534 carboxylation, 528, 532 ethanolysls, 531 formylation, 528-534 halogenation, 27-53 reactions, 467-555 see also Phenols 0-Resorcylic acid, 537 Rhodoporphyrins, isotopic labelling, 192 Ribonucleases, in enzymic synthesis of oligonucleotides, 318-319 Ribooligonucleotides, in synthesis of oligonucleotides, 311-313 Rifamycin B, 435 Ring compounds containing oxygen, 467555 Ring contraction, of chromenes, 517,518 of cyclohexenes, 360 Ringexpansion, by migration to exocyclic carbonium centre, 29 of thiazolidines, 345 RNA Polymerase, in enzymic synthesis of 591 oligonucleotides, 316-31 Rosenmund reduction, of acid chlorides, 21, 58 Rotenoids, 498-5 13 Rotenone, 498 Rothemund reaction, in synthesis of porphyrins, 150 Rotiorin, 531 Rotoxen, 498 Rubropunctatin, 53 Ruff degradation, of hydroxy acids, 22 of hydroxylactones, 22 Salicylic acids, Nencki reaction, 535-539 xanthone formation, 535-539 Saramycetin, 404 Schiff s bases, 202 as intermediates in porphyrin synthesis, 169 Schmidt degradation, urethane formation, 215 Sclerotiorin, 526, 527 Selective hydrolysis of acetonides, 138 of esters, 133 Selective reduction, of esters, 133 with sodium borohydride 133 Selenium dioxide, in dehydrogenation, 44 as oxidising agent, 488 Selinetin, acid-catalysed rearrangement, 478 Sephadex gel filtration, in chromatography of oligonucleotides, 305, 308 Serratamolide, 406 Serratia marcescens pyrrole content, 227 1,ZShift of acyl group in acylvinylamines, 236 Silica gel, as acid catalyst in rearrangement of ally1 ethers, 553-554 in chromatography of oligonucleotides, 304 Silver oxide, as condensing agent, 549 Silyl ethers, directing effect, in borohydride reduction, 18 in hydrogenation, 133 as protecting group for alcohols, 134, 136 Sodium bisulphate, as dehydrating agent, 476 Sodium dithionite, as reducing agent, 345, 403,438 Sodium periodate/osmium tetroxide, as oxidising agent, 493 592 Subject Index Sorbus aucuparia, extraction of L-parasorbic acid, 22 Spiramycin, sugar moiety, 48, 52 Spirographis spallanrani, porphyrin moiety of heme, 189 Sporidesmolide-I, 406 Stabilised carbanions, 59; see also Acetylenic carbanions; Aldol condensations; Carbanionic Reactants; Crignard reactions; Malonic ester syntheses Staphilomycins, 404 Stereospecific hydration, of olefins, 91 Sterigmatocystin, 485 Strecker reaction, 338 Streptomyces antibioticus, 19 Streptonigrin, 435 Streptovitacin A, 435 Styrenes, hydroxylation 525 &Substituted esters, displacement reaction, 34 Sugars, see Carbohydrates Sulphide contraction, in inter- and intramolecular reactions, 241-261 Sulphoxides, 345 reduction, 345 in ring expansion of thiazolidines, 345 Sulphuryl chloride, as halogenating agent, 157, 185 as oxidising agent, 165 Swartzia madagascariensis, 52 Symphonia globulifera, 544 L-Tartaric acid, as carbohydrate precursor, 19-24 reduction, 20 I , 1,2,2-Tetracarboxylic esters, reductive cleavage, 235 Tetracyclines, 348-364 Tetradehydrocorrins, hydrogenation, 232 2-Tetrahydrofuranyl ethers, 31 Tetrahydrofurobenzofurans,488 Tetrahydropyranyl ethers, as protecting group for alcohols, 96-138, 291 Tetrahydropyrones, 429 Grignard reaction, 429 Tetrahydroxybenzoquinone,hydrogenation, 68 Tetramethylammonium hydroxide, as condensing agent, 541 Thallium 111, as oxidising agent, 512 Thallium hydroxide, as condensing agent, Thiazines, 342-348 isomerisation, 345 Thiazoles, addition with azidoketene, 341 in synthesis of penicillins, 34 Thiazolidines, 337-343 cleavage, 345 as protecting group for a-aminothiols, 342-345 ring expansion, 345 substitution, 343 Thiazolines, addition with azidoketene, 341 Thiazolones, 360 cleavage, 363 as protecting group for aldehydes, 362 Thioacetals, 382 Thioamides, hydrolysis, 363 methylation, 363 as protecting group for amines, 363 Thiobenzoyl glycine, thiazolone formation, 360 Thioethers, as carbanionic reactants, 343 cleavage, 393 Thioformylpyrromethanes, 202 reactivity, 202 Schiffs base formation, 202 1-Thioglycosides, 27,28 Thiohemiacetals, 343 Thioimino ethers, hydrolysis, 363 as intermediates in thioamide hydrolysis, 363 Thiolactams, 24 1-26 addition with olefins, 241 condensation with methylenepyrrolidones, 241-261 in synthesis of corrins, 241-261 vinylogous amidines, 241-261 Thiolactones, 257 ring cleavage to amides, 258 Thiols, 338,347 Titanium tetrachloride, as catalyst for Fries rearrangement, 442 Tosyl amides as protecting groups for amines, 409-426 Tosylates, displacement by azide ion, 343, 378 halogenation, 382 reductive cleavage, 54, 378 Tosylation, of polyalcohols, 376, 378, 382, 395 Subject Index Tosyl chloride/collidine, as dehydrating agent, 478 N-Tosylglycines, condensation with a$unsaturated ketones, 153 Trialkyl oxonium salts, in synthesis of corrins, 234-245 imino ethers, 234-245 vinylogous amidines, 234-245 Trichloroethyl esters, as protecting group for carboxylic acids, 89, 345 phosphate, 291 Trichloromethylsulphenylchloride, addition to vinyl ethers, 34, 35 Tricyclooctanes, 47 2,3,4,-Trideoxypentopyranose,equilibrium with l,S-hydroxyaldehydes, 28, 29 1,3,5,-Trienes, cyclisation, 202 Triester approach, in synthesis of oligonucleotides, 304 Triethylammonium acetate, as dehydrating agent, 360 Triethyi orthoformate, in synthesis of acetals, 487 Trifluoroacetic anhydride, as condensing agent, 532 Trifolirhizin, 524 2',4',7-Trimethoxyisoflavone, Trimethyl orthoformate, condensation with b-bilene-l',8'-dicarboxylicacid, 185 b-bilenes, 195, 197 b-oxobilane-1',8'-dicarboxylicacids, 187, 189,191 1,3,4,-Triols, protection as and regeneration from orthoesters, 395 Trioxymethylene, condensation, Tripyrrylmethanes, as interrnidiates in pyrromethane synthesis, 168 side-products from b-bilene cyclisation, 197 Tritylamines, as protecting groups for amines, 341,347,409426 Trityi ethers, as protecting group for alcohols, 400, 402 Tubaic acid, 505, SO6 Tubanol, 503 Tyrocidins, 404 Tyrothricin, 406 Ubichromenol, 476 Ubiquinone, rearrangement to 593 ubichromenol, 476 Ullman synthesis, of aryl ethers, 539 Umbelliferone, 470 Umtatin, 512 a,P-Unsaturated acids, addition of amines, 35 P,y-Unsaturated acids, alkylation, 267 bromolactonisation, 265 ?-Unsaturated acids, cyclopentenone formation, 488,490-494 halolactonisation, 18,71, 91, 108 a,P-Unsaturated aldehydes, 345 1,2-addition, 480 1,rl-addition of amides, 345 addition with carbanionic reactants, 100 Diels-Alder reaction, 30,4 1, 43 reaction with alkylating agents, 1 Reformatsky reaction, 18 a,@-Unsaturatedamides, 250 Michael reaction, 250 see also Pyridones; Pyrrolinones Unsaturated, deoxy, I-thiosugars, 27, 28 qb-Unsaturated esters, 235, 239, 345 addition of HCN, 268 nitroalkanes, 268 condensation with a-amino esters, 230 decarboxylation, 235, 239 Diels-Alder reaction, 30, 70-72, 236 halogenation, 345 cis-hydroxylation, 54 Michael reaction, 238, 351 from pyrolysis of 0-acetoxyesters, 71 P,T-Unsaturated esters, 439 a$-Unsaturated hemi-ketals, 505 hydrogenation, 505 a,P-Unsaturatedy-keto esters, Diels-Alder reaction, 245 halogenation, 132 hydrogenation, 133 a$-Unsaturated-keto-ketones, base catalysed cleavage, 444 a,P-Unsaturated ketones, addition with HCN, 124,232,262 nitroalkanes, 264 condensation with N-tosylglycines, 153 cyclopropane formation, 509 dehydrogenation, 441 Diels-Alder reaction, 483 epoxidation, 231 with Crignard reagents, 125 594 Subject Index Michael addition, 357,444 oxidative cleavage, 251, 254 photochemical 1,2-~ycloaddition,125 reduction, 56, 501-504, 509 reductive rearrangement to allylic alcohols, 23 a,p,yUnsaturated ketones, 47 1-475.480 485 cyclisation to chromenes, 471-475,48& 485 Diels-Alder reaction, 554 a$-Unsaturated nitriles, 235, 239,439,452, 526 condensation with iminoethers, 237, 239, 24 pyrrolidones, 244 Diels-Alder reaction, 30, 93, I08 hydrogenation, 452 a$-Unsaturated nitroalkanes, 385 addition of ammonia, 385 Diels-Alder reaction, 97 0,r-Unsaturated ylids, addition of nitroalkanes, 101 Ureas, 380 nitrosation, 380 Urethanes, as protective precursors of vinyl groups, 15 from Schmidt degradation, 215 Valinomycin, 406 Verdohemes, 11 Vilsmeier condensation, of pyrroles, 230 of pyrrolidones, 230 of 2-pyrrolinones, 230 in synthesis of bipyrroles, 230 Vilsmeier-Haack procedure, formy lation of pyrrolylmethylenepyrrolinones,2 pyrrolylmethylpyrrolinones,21 Vinyl amines, 230,234,261,439 addition with nitroalkanes, 238 cyclisation to thiazines, 347 in synthesis of vinylogous amidines, 234245 Vinylation, of aromatic compounds, 476 Vinylcoumaranones, 509-513 rearrangement, 509-51 Vinylene carbonate, Diels-Alder reaction, 67,68 Vinyl esters, Diels-Alder reaction, 70, 71 NOCI addition, 51, 377 Vinyl ethers, 377,395,429,433,444,467555 from acetals, 41 acid-catalysed cyclisation, 43 addition with NOCI, 51, 52, 377 quinones, 487 sulphuryl chlorides, 34, 35 alcoholysis, 429 amination, 52 aminoalkoxylation, 52 cleavage, 230 condensation with a-amino esters, 230 Diels-Alder reaction, 30, 41 displacement of alkoxide by amines, 230 epoxidation, 31 haloalkoxylation, 34, 35, 40, 41 halogenation, 32,34,48 from hemiacetals, 47, hydroboration, 41,49, 52 hydrohalogenation, 32, 34 hydroxyhalogenation, 32 cis-hydroxylation, trans-hydroxylation, 32 oxidative cleavage, 433 ozonolysis, 256 reduction, 501, 502, 504,509 in synthesis of thiazolidines, 339 Vinylethynylketones, 446 double Michael addition, 445 Vinyl group, protection as and regeneration from urethanes, 215 Vinyl halides, condensation with phenols, 494 reduction, 550 in vinylation of aromatic compounds, 476 Vinyl lactones, addition of NOCI,51, 377 Vinylogous amidines, 234-26 in synthesis of corrins, 234-261 Vinylogous hemi-ketals, oxidative cleavage, 265 Vinyl thio-ethers, 345 Vinyltriphenylphosphonium bromide, 456 Viomycin, 404 Vitamin B,,, 232-268 Wanslick coupling, of catechols, 516-521 of hydroxycoumarins, 516-521 Wessely-Moser rearrangement, of xanthones, 535 Wittig reaction, of a-aminoketones, 439 Subject Index of enolates, 120 of hemiacetals, 92, 109, 114 in synthesis of cis-olefins, 92, 109, 114, 383 fruns-olefins, 81-1 38 &r-unsaturated esters, 439 vinylamines, 439 under very mild conditions, 530 Wolff rearrangement, of diazoketones, 20 Woodward’s reagent, in synthesis of p e p tides, 422 Xanthones, 495-5 13,534-555 cleavage, 499 formylation, 547 595 halogenation, 546 hydroxylation, 547 oxidation, 547 substitution, 534-555 Wessely-Moser rearrangement, 535 Xanthyletin, 478 Xanthyllum salts, as intermediates in synthesis of xanthones, 546 Zinc carbonate, as condensing agent, 494 Zinc chloride/phosphoryl chloride as condensing agent, 535-9,548 Zinc/Copper, in specific cleavage of trichloroethyl esters 291 Total Synthesis OfNatural Products, Volume1 Edited by John Apsimon Copyright © 1973 by John Wiley & Sons, Inc Reaction Index 3-Acetamido-2,3dideoxy-D-tetrose, 58 3-Acetamido-2,4,6-tri4-benzyl-3deoxya-Dglucopyranosyl chloride, 369 a-Acetoxy-protoporphyrin-IX dimethyl ester, 178 I-Acetylbchloroquinide, 70 4-Acetyla-hydroxydeuteroporphyrin-IX, 178 N-Acetyl lincosamine, 385 Acronycine, 476,484 Acronylin, 475 a-Acrosazone, a-Acrose, a-Acrosone, Actinomycin D,419422 Aetioporphyrins, see etioporphyrins Aflatoxin B, ,486,490,491 Aflatoxin B, ,486,488 Aflatoxin G , ,494 Aflatoxin M,,486,491494 Ageratochromene, 469,471,476477 Alanine t-RNA gene, 321-324 Alleovodionol, 475 methyl ether, 473474 Allitol, 9, 10 DL-AUose, 72 up-DL-Allose, 45 Alvaxanthone, 553 7-Aminocephalosporanic acid, 345 5-Amino-5deoxya-Dalofuranuronic acid, 400 2-Amino-2deoxy4,54-isopropylidene- D-pentanoic acid, 60 5-AminoJ,6dideoxy-DLallonic acid, 25 5-Amino-5,6dideoxy-DL-gulonic acid, 27 2-Amino-3,3dimethyl4-hydroxybutyraldehyde, 60 DLsrythro-4 -Amino-5-hydroxyhexanoic acid, 51,377 2-Aminomethyl-3,5-bis(carboxylmethyl)pyrrole, 159 2-Aminomethyl-3carboxyl methyl pyrrole, 159 6-Aminopenicillanic acid, 341 4-Amino-2,3,4-trideoxya-D~rythrohe~- 2-enpyranosiduronic acid, 403 erythro-2-Amino-l,3,4-trihydroxybutane, 19 Ampicillin, 338 Angustmycin A, 388,394 1,4-Anhydro-cis-conduritol carbonate, 67 1,6-Anhydro4deoxy6-DL-ribo-hexopyranose, 46 1,6-Anhydr0-3deoxyS-DL-ribo-hexopyranose, 45 1,6-Anhydro4deoxyQ-DL-xy/o.hexopyranose, 1,6-Anhydro4deoxy-3-O-methylQ-DLxylo-hexopyranose, 54 1,6-Anhydro3,4dideoxyQ-DL-erytbrohex3enopyranose, 43 1,6-Anhydro-3,4dideoxyQ-DL-erythro597 598 Reaction Index hexopyranose, 46 1,6-AnhydroQ-DL-glitco-hexopyranose, 45 1,6-Anhydro-3C)-met hylQ-DL-ghco-hexopyranose, 45 Anthramycin, 434,437440 D-Apionic acid, Apiose, L-Apiose, 22 Aposclerotiorin, 530 DL-Arabinitol, 11 DL-Arabinose,6, 13,14 Arthothelin, 546 Ascochitine, 528 Aversin, 496 methyl ether, 486 Beauvericin, 422424 BeUadifolin, 547 5~-Benzyl-2,3dideoxy-D-pentofuranose, 24 DQ-Benzyloxydecanoic acid, 425 a-Benzyloxyprotoporphyrin-IXdimethyl ester, 178 truns-3-BenzyIthio-2chlorotetrahydropyran, 35 5-Benzylthio-3,4dihydro-2H-pyran, 34, 35 lruns-3-Benzylthio-2-rnethoxytetrahydropyran, 34,35 Bilirubic acid, 21 Bilirubin, 213,215 Biliverdin-IXa, 210,212,213,215 Biliverdin dimethyl ester, 179 N,N’-Bis(carbobenzyloxy)-2deoxystreptamine, 369 N,N-Bisdemethylterramycin, 363 Blasticidin S, 404 3-BrOmO-S,6dihydro4H-pyran, 3a-Bromo-2a,4pdknethoxytetrahydropyran, 38 3cr-Bromo-2a,Sadime t hoxytetrahydropyran, 42 3P-Bromo-2a,4adirnethoxytetrahydropyran, 38 ~runs-&cis-4-Bromo~,8dioxabicyclo [ 3.2.1 ] octane, 43 3-Bromo-2ethoxy-5.6dihydro-ZH-pyran, 39 Buchanaxanthone, 551,552 2-t-Butoxy-3,4epoxytetrahydropyran, 36 2-1-Butoxy-3-hydroxytetrahydropyran, 36 But yl cis4-acetoxy-5,6 dihydro4 H-pyran 6-carboxylic acid, 40 Butyl trans-2-acetoxy-5,6dihydro-2H-pyran 6carboxylic acid, 40 Butyl truns4-acetoxyJ,6dihydro4H-pyran 6carboxytic acid, 40 Qnnabichromene, 473474,481 Cannabicyclol, 483 N-CarbobenzyloxydesformylgramicidinA, 409 N-Carbobenzyloxypurornycin,394 5-Carboethoxy4ethoxyacetyl-3ethoxypropionyl-2-methylpyrrole, 155 2,30-CarbonylnoviosyI chloride, 448 3-Carboxyethyl-2,5dimethylpyrrole.150 5-Carboxyethyl-2,3dimethylpyrrole,153 2-Carboxyethyl-5-rnethylpyrrole,152 6-(Carboxymethyl)acetylrhodoporphyrinXV dimethyl ester, 191 Cephaloridine, 345 Cephalosporins, 342-348 Cephalosporin C, 345 Cephalosporin-V, 345 Cephalothin, 345 DL-Chalcose, 53 Chlorine, ,202 Chlorin-e,, 169,202 Chloroamphenicol, 434,457458 Chlorocruoroporphyrin, 182 3-CNoro-5,6dihydro4H-pyran, 32 2-@-Chloroethoxy)-3-hydroxytetrahydropyran, 4p-Chloro-3aethylthio-2p-methoxytetrahydropyran, 38 Iruns-2-Chloro-3ethylthiotetrahydropyran, 35 truns-2-Chloro-3-methylthiotetrahydropyran, 35 DL-Cinerulose A, 56 Citrinin, 532 Citrylidenecannabis, 483 Clausenin, 476477 Cobyric acid, 270 Conduritol-C, 67 Coproporphyrin-I, 170, 174 Reaction Index Coproporphyrin-11, 167,169, 174 Coproporphyrin-111,174,187 tetramethyl ester, 187 Coproporphyrin-IV, 174,187 Cordycepin, 387,398 a-Corrnorsterone, 254 0-Corrnorsterone, 254 Coumestrol, 515,518 Coumurrayin, 472 Curvularin, 427429 Cycloheximide, 434,451454 Cycloserine, 434 Deguelin, 501 Dehydrodeguelin, 501 Dehydroelliptone, 509 15-Dehydroprostaglandin E, , 122-124 Dehydrorotenone, 505-506 Demethylsuberosin, 47 D-Dendroketose, LDendroketose, 12a-Deoxy-5a,b-anhydrotetracycline,356 5-Deoxy-DL-arabinonic acid, 23 6-Deoxy-6demethyltetracycline, 349,35 1, 353,359 3-Deoxyepiinositol, 368 2-Deoxy-2-fluoro-DLerythritol,6 2-Deoxy-2-fluoro-DL-ribitol,6 2-Deoxy-2-fluoro-DL-threitoI,6 2-Deoxya,O-DLribo-hexopyranose, 46 3-Deoxy-DLribo-hexopyranose,45 4-Deoxya&DL-ribo-hexopyranose, 46 6-Deoxy-D~robino-hexulose, 64 6-Deoxy-L-xy/o-hexulose, 64 2-Deoxy-3,44l-isopropylidene-DLallitol, 73 Deoxyjacareubm, 552 5-methyl ether, 552 3-Deoxy-2-keto-D-pentaric acid, 64 1-Deoxy-DL-lyxitol, 23 2-Deoxy-D+rythro-pentose, 15 2-Deoxy-L-erythro-pentose,17 2-Deoxy-DL-erythro-pentose,16-18 4-Deoxy-DLerythro-pentose, 47 2-Deoxy-DLthreo-pentose, 17 1-Deoxy-DLribitol, 23 5-Deoxy-DLribonic acid, 23 2-Deoxy-D-ribose, 15 4-Deoxy-DL-ribose, 46,47,73 2-Deoxystreptamine, 368 599 3-Deoxy-2-tetrulosonicacid, 64 2-Deoxy-D-xylose, 14,17 Derrisic acid, 503 DL-Desosamine, 47 Desoxophylloerythroetioporphyrin,197, 198 Deuteroporphyrin-IX, 170 cis-3,6-Diacetoxycyclohexene4-carboxylate, 2,4-DiacetylaacetoxydeuteroporphyrinIX,178 Di4-acetyl-2deoxy-Lrhreo-pentaric acid dimethyl ester, 20 Di4-acetyl tartaric anhydride, 20 1,6 :2,3-Dianhydro4deoxyQ-D Llyxohexopyranose, 43 1,6:2,3-Dianhydro4deoxyQ-DLribohexopyranose, 43,46 5,6-Dianhydro-2ethoxyb-rnethyl-2H-pyran, 48 1,6 :3,4-DianhydroQ-DLallo-hexopyranose, 43 3a,4~-Dibromo-2aethoxytetrahydropyran, 38 3a,4P-Dibromo-2Pethoxytetrahydropyran, 38 3,5-Dicarboxyethyl-2,4dirnethylpyrrole, 150 6,7-Di(carboxymethyl)methyI-2,3dimethyl1,4,5,8-tetra(carboxymethyI)ethylporphyrin, 169 5,6-Dideoxy-DL-ribo.hexitol, 54 4,6-Dideoxy-Lribo.hexonicacid, 1,5-lactone, 22 5,6-Dideoxy-D~ibo-hexonic acid lactone, 54 3,4-Dideoxya$-DL.-erythro-hexopyranose, 46 2,3-Dideoxya,O-DL-eryrhro-hexose,4 5,6-Dideoxy-D-threo-hexulose, 64 4,6-Dideoxy-34l-methyl-D-xylo-hexose, 54 3,5-Dideoxy-L-erythm-pentose,22 2,3-Dideoxy-DL-pentose, 18 cis-2,S-Diethoxy-5,6 dihydro-2H-pyran, 39 rrans.2,5-Diethoxy-5 6dihydro-2H-pyra11, 39 trons-5,6-Diethoxy-5,6dihydro-2H-pyran, 39 Dihydrocitrinin, 533 600 Reaction Index 2,3-Dihydrofuran, 29 Dihydroisoneobilirubic acid, 222 Dihydro4-methylsterigmatocystin,495 Dihydroneobilirubic acid, 219 7,8-Dihydro7-phyUoporphyrinXV, 199 d,l-13,14-DihydroprostaglandinE , , 118-122 3,4-Dihydro-2H-pyran, 29 1,3-Dihydroxy-7-methoxyxanthone, 53 1,3-Dihydroxypropanone, trimethyl ether, 475 Flindersine, 480 Formose, 2-Formyl-3,4dihydro-2H-pyran,30 2-Formyl4-vinyldeuteroporphyrin-IXdi- methyl ester, 189 DL-Forosamine, 52 Franklinone, 475 D-Fructose, 4,64 cis-2,5-Dimethoxy-5,6dihydro-2H-pyran, L-Fructose, 42,46 Fuscin, 532 cis-2,5-Dimethoxyd-methyltetrahydropyran, 41 trans-2,5-Dimethoxyd-methyltetrahydropyran, 2,4-Dimethoxytetrahydropyran, 36 cis-2,5-Dimethoxytetrahydropyran,4 truns-2,5-Dimethoxytetrahydropyran,4 PJ3-Dimethylmethylenebutyrolactam,235 6,8-Dioxabicyclo [3.2.1] octane, 43 6,8-Dioxabicyclo 13.2.1 oct-2-ene 43 6,8-Dioxabicyclo [3.2.1] oct-3ene, 43 Divinylglycol, 2.4-Divinylrhodoporphyrin-XVdimethyl ester, 189 Elliptic acid, 509 DL-Epimycarose, 62.64 6-Epipenicillin-V methyl ester, 342 3,4-Epoxy-2-methoxytetrahydropyran,36 Erosnin, 521 Erythritol, 17 D-Erythrose, 19 Ethyl 4-amino4deoxya-DL-lyxopyranoside, 60 4-Ethyl-2cyclododecenol, 23 5-Ethylthio-3,4dihydro-2H-pyran, 34.35 trans-3-Ethylt hio-2-met hoxy te t rahydropyran, 34,35 Etioporphyrin-I, 170, 173, 179 Etioporphyrin-II, 167, 169,173 Etioporphyrin-Ill, 173 Etioporphyrin-IV, 173 Euxanthone, 538 Evodionol, 475 methyl ether, 471,484 Flcmingin A, 483 Flemingin B, 483 Flemingin C, 483 Galactitol, 10 a#-DLGalactose, 45 Gentisein 543 Girinimbine, 485 DGluconic acid, D-Glucose, DLClucosc, 43 DLGlucosone, Glutarimide-3-acetic acid, 451 Gramicidin S,4 12 Griseofulvic acid, 444 Griseofulvin, 434,440447 epi-Griscofulvin, 444 Griseoxanthone C, 546 Harderoporphyrin, 192 Hemin, 170 Hesperimine, 256 D-clrabino-Hexosephenylosazone, DLarabino-Hexose phenylosazone, D-arabino-Hexosulose, DLarubino-Hexosulose, D-arubino-Hexulose, D-xylo-Hexulose, I-Hydroxy-5-bromo-3-oxabicyclo [ 3.2.1 ] octan-2-one 71 7-Hydroxy-l l ,I 2dimethoxycoumestan, 519 3-Hydroxy-8,9dimethoxypterocarpan, 522 3-Hydroxy-2-methoxytetrahydropyran, 36 cis & trons-S-Hydroxy-2-methoxytetra- hydropyran, 41 2-Hydroxymethyl-3,4dihydro-2H-pyran, 43 Hydroxymethylglyceraldehyde, Hydroxymethylglycerol, Reaction Index 4C-HydroxymethyI-Dglycero-pentulose, 1-Hydroxy-2,3,4,7-tetramethoxyxanthone, 54 Ileu-Gramacidin A, 407409 Inermin, 524 do-lnositol, 68 epi-lnositol, 68 myo-lnositol, 68 neo-lnositol, 68 Isobilirubic acid, 213 Isocannabichromene, 48 a-epi-Isocycloheximide, 45 Isoelliptone, 509 Isogriseofulvin, 444 lsoneoxanthobilirubic acid, 19 Isonovobiocin, 448 Isopemptoporphyrin methyl ester, 187 Isorotenone, 51 Isoxanthobilirubic acid, 213 601 Medicagol, 518,519 Mesobilirhodin, 215 Mesobilirubin-IXa, 194,214 Mesobilirubin-XIlb, 214 Mesobiliverdin-IXa, 212 Mesobiliverdin-IW, 212 Mesobiliviolin, 215, 218 Mesoporphyrins, 173 Mesoporphyrin-IV dimethyl ester, 195 Mesoporphyrin-IX, 181 dimethyl ester, 185,187 Mesoporphyrin-X dimethyl ester, 195 Mesoporphyrin-XI dimethyl ester, 187 Mesoporphyrin-XI11dimethyl ester, 195 Metacycloprodigiosin, 231 Methicillin, 338 Methose, 2-Methoxy-3,4dihydro-ZH-pyran, 41 2-MethoxyJ,6dihydro-ZH-pyran, 46 3-Methoxy-3,4dihydro-2H-pyran, 41 7-Methoxy-2,2dimethyIchromene,47 8-Methoxyhomopterocarpin,5 24 Jacareubin, 484,549 trans-2-Methoxy-6-methoxymethyl-5,6- Kanamycin A, 372 Kasugamine, 51 Kasugamycin, 377 Kasuganobiosamine, 53,378 Keto-D-psicose pentaacetate, 394 trans-2-Methoxy-3-methylthio-tetrahydro- dihydro-2H-pyran,41 Lankavose, 53 Lapachenole, 468,469 ' Lichexanthone, 535 Lincomycin, cis-lincomycin, 381 Lonchocarpine, 470,484 Lucernol, 515 Luvungetin, 470,471 DL-Lyxose, 13 Maackiain, 521-522 new-(T)-Magnesium protoporphyrin-IX, 192 Mahanimbine, 483 Mangiferin, 548 DL-Mannitol, 4,9 DMannonic acid, LMannonic acid, D-Mannose, L-Mannose, pyran, 34,35 4-Methoxypterocarpin,522 3-Methoxypyrrole-2-carboxylicacid, 230 truns.2-Methoxy-3-(trichloromethylthio)- tetrahydrofuran, 34 Methyl(~)-3-O-acety14,50-isopropylideneshikimate, 71 Methyl 2,3-anhydro4deoxyd-O-methyla-D L-lyxo-hexopyranoside, 40 Methyl 2,3-anhydro4deoxyd0-methyla-DLribo-hexopyranoside, 40 Methyl 50-benzyl lyxfuranoside, 24 Methyl 5-O-benzylQ-D-ribofuranoside, 24 Methyl Dkymaroside, 49 Methyl 4deoxy-DL-hexopyranoside, 40 a-,& p-Methyl4deoxy-30-methyl-DL xylo-hcxopyranoside, 54 Methyl 4deoxy-30-methyla-DLthreopentopyranoside, 36 Methyl 4deoxy-30-methyl$-DLthreopentopyranoside, 36 Me thy1 4deoxyQ-Dhrythro-pentopyranoside, 46 Methyl 3deoxyQ-D-ribofuranoside, 398 des-Methyl deuteroporphyrin IX, 174 602 Reaction Index Methyl @-2$-5diacetoxya-3,a4-dihydroxycyclohexylcarboxylate, 71 Methyl 2,3di43-acetyi-Sdeoxy-Lthreo4-pentulosonate, 20 Methyl 2,3di43-acetyl-543-ethyl-Lthreo4-pentulosonate, 20 Methyl 2,3di.O-acetyl-L-theuronate, 20 a- & &Methyl 4,6dideoxy-343-methyl-20-p-tolylsulphonyl-DL-xylo-hexopyranoside, 54 Methylenitan, Methyl-Dhpimycaroside, 62 34-Methyla,r3-DL-glucopyranose,45 N-Methylglucosamine, 365 34l-Methyl-DLglucose, 45 Methyl 2,343-isopropylideneQ-DL-allofuranoside, 73 Methyl DL-kasugaminide, 51 443-Methyl-DL-lyxose, 46 Neodulin, 524 Neoisoxanthobilirubic acid, 21 Neoxanthobilirubic acid, 213,214,219 p-Nitrophenylserine methyl ester, 457 Norlichexanthone, 535 Noviose, 448 Novobiocin, 434.447450 Octaethylchlorin, 199 Octaethyl-7,8dihydroxychlorin,210 Osajaxanthone, 548 Osthenol, 472 4-Oximino-5axohexanoic acid, 51,377 Oxytetracycline, 359 Pemptoporphyrin, I82 dimethyl ester, 189 D-Penicillamine, 338 Penicillins, 337-348 cis-3-Methyld-methoxycarbonyl-3,6dihy- Penicillin V, 341 dro-l,2axazine hydrochloride, 25 D-threo-Pentulose, 64 Methyl 443-methylaDL-arabinopyranoPheophorbidea, 206 side, 42 7-Phyllochlorin-XV, 199 Methyl 343-methyla$-DLglucopyranoPhylloporphyrins, 176 side, 45 Phylloporphyrin-XV, 173, 181 Methyl 4-O-methyla-DL-lyxopyranoside, DL-Picrocin, 47 41 Pisatin, 524,525 Methyl DLmycaminoside, 48,49 Polygalaxanthone-B, 547 Methyl DL-mycaroside, 62 Polymixin 9, ,416 Methyl DL-oleandroside, 49 Pongachromene, 470 Methyl (W)-shikimate, 72 Porphobilinogen, 155-158 Porphyrina, 169 0-Methylsterigmatocystin, 495 Preremirol, 475 5-Methylthio-3,4dihydro-2H-pyran 34, Prodigiosin, 227 35 Methyl a-thiolincosaminide, 382 Prostaglandins, 81-138 Methyl 2,3,5-tri-O-acetyl4.4'-anhydro4Prostaglandin E, 89-118 C-hydroxymethyl-L-threo-pentonate, d,f-Prostaglandin E, methoxime, 132-133 22 Prostaglandin F, 89-118 Methyl 2,3,5-tri-0-acety14-pentulosonate, Protoporphyrin-IX, 170,182,187 22 dimethyl ester, 187 Methyl triO-acetyl-Lthreonate, 20 Psicofuranine, 388,394 Mitomycin C, 455457 Psicose, 388 Mtorubrin, 532 D-Psicosyl chloride, 394 Monomethyl die-acetyl-L-tartrate, 20 Psoralidine, 15 Munduseran, 505 Pterocarpin, 522,524 Munduserone, 500,509 Puromycin, 388,390 DL-Mycarose, 62,64 Pyrroporphyrins, 174 Pynoporphyrin-XV, 173 Nafcillin, 338 Pyrroporphyrin-XVIII, 179 Neocycloheximide, 453 Reaction Index (-)Quinic acid, 70,71 (?)-Quinide, 71 Rhodin-g, ,209 Rhodoporphyrin, 169 Rhodoporphyrin-XV, 173, 181 dimethyl ester, 189,191 Ribitol, 1 Ribose, D-Ribose, 24,64 DL-Ribose, 13-15,73 Rotenone, 503-504 Sangivamycin, 388,398 Sativol, 515 Sclerotioramine, 526 Scriblitifolic acid, 551 Serratamolide, 424426 Seselin, 470,471 Shikimic acid, 71 Siccanochromen A, 478 L-Sorbose, 64 Stercobilin, 218 Stercobilin-IIIa, 222 Stercobilin-Xllla, 219 Sterigmatocystin, 485498 Streptidine, 365 Streptose, 365 Streptozotocin, 380 Terramycin, 359 Tetracycline, 356 Tetrahydropyrano [ 2,341-1,4-dioxane, 31 Tetrahydrosclerotioramine, 527 Tetrahydrosclerotiorin, 529 1,3,4,5-Tetrahydroxy-l cyclohexanecarboxylic acid, 70 ‘letramethoxycoumestan, 515 1,2,3,7-Tetramethoxyxanthone,540 Tetrose, Tetrulose, DL-glycero-Tetrulose, 19 3-endo-Thiomet hyl-3-exo.cyano-2-thiobicyclo (2.2.1.1 hept-Sene, 28 Thiophanic acid, 546 L-Threitol, 20 DL-Threitol, 17 603 L-Threonic acid, 21 L-Threono-l,4-lactone, 20 D-Threose, 19 Thuringion, 546 Toyocamycin, 388,398 3,4,6-Trideoxy-3dimethylamino-D-xylohexose, 47 2,3,6-Trideoxya-DL-hex-2enopyranos4ulose, 56 2,3,6-Trideoxy-L-glycero-hexopyranose4ulose, 56 Trifoliol, 519 3,8,9-Trimethoxypterocarpin,522 Tubercidin, 388,398 Tyrocidine A,412413 Tyrothricin, 406413 Ubichromenol, 476 d-Urobilin, 225 Wrobilin, 218 Urobilin-111, 226 Urobilin-IXa, 215,226 Urobilin-XIII, 226 Uroporphyrin-I, 174 Uroporphyrin-I1,167,169,174 Uroporphyrin-Ill, 169, 174 Uroporphyrin-IV, 169,174 Valgramicidin A, 407409 4-Vinyldeuteroporphyrin-IXdimethyl ester, 189 2-Vinyldeuteroporphyrin-IXmethyl ester, 187 2-Vinylrhodoporphyrin-XV dimethyl ester, 189 Vitamin B,, ,270 Wedelolactone, 514-516 Xanthobilirubic acid, 213,214 Xanthoxyletin, 476 Xanthyletin, 470 DL-Xylose, 6,13 Yeast alanine t-RNA, gene, 321-324 Zearalenone, 427634 ... The Total Synthesis of Antibiotics 3 31 F JOHNSON The Total Synthesis of Naturally Occurring Oxygen Ring Compounds 467 F M DEAN Subject Index 563 Reaction Index 597 ix THE TOTAL SYNTHESIS OF NATURAL. .. JONESand W A SZAREK The Total Synthesis of Prostaglandins u AXBN,J E PIKE, AND w P SCHNEIDER The Total Synthesis of Pyrrole Pigments 81 143 A H JACKSON AND K H SMITH The Total Synthesis of Nucleic Acids... TOTAL SYNTHESIS OF NATURAL PRODUCTS Total Synthesis OfNatural Products, Volume1 Edited by John Apsimon Copyright © 19 73 by John Wiley & Sons, Inc The Total Synthesis of Carbohydrates J K N JONES