Preface ........................................................ xi
Abbreviations ................................................ xiii
1 Introduction—Biofunctional Molecules and Organic Synthesis ... 1
1.1 What are biofunctional molecules? ....................... 1
1.2 Developmental stages of studies on biofunctional
molecules ............................................... 1
1.3 Small amounts of the samples are now sufficient for
the elucidation of the structures of biofunctional
molecules ............................................... 3
1.4 Why must biofunctional molecules be synthesized? ........ 4
1.5 How can we synthesize biofunctional molecules? .......... 5
1.5.1 What is synthesis? ............................... 5
1.5.2 What kind of consideration is necessary before
starting a synthesis? ............................ 5
1.5.3 Synthon .......................................... 6
1.5.4 Molecular symmetry and synthesis ................. 6
1.5.5 Criteria for 'A Good Synthesis' .................. 6
1.6 What kind of knowledge and techniques are necessary
to synthesize biofunctional molecules? ................. 10
1.6.1 Stereochemistry and reactivity .................. 10
1.6.2 Stereochemistry and analytical methods .......... 11
References .................................................. 16
2 Synthesis of Phytohormones, Phytoalexins and Other
Biofunctional Molecules of Plant Origin ..................... 19
2.1 Phytohormones .......................................... 19
2.1.1 What are phytohormones? ......................... 19
2.1.2 Gibberellins .................................... 20
2.1.3 Diterpenes related to gibberellins .............. 30
2.1.4 Abscisic acid and its relatives—synthesis of
optically active compounds ...................... 38
2.1.5 Brassinosteroids ................................ 41
2.1.6 Phyllanthrinolactone, a leaf-closing factor ..... 45
2.2 Phytoalexins ........................................... 49
2.2.1 What are phytoalexins? .......................... 49
2.2.2 Synthesis of pisatin ............................ 49
2.2.3 Synthesis of 2-(4-hydroxyphenyl)naphthalene-
1,8-dicarboxylic anhydride ...................... 52
2.2.4 Synthesis of oryzalexins ........................ 53
2.2.5 Synthesis of phytocassanes ...................... 56
2.3 Plant allelochemicals .................................. 59
2.3.1 Synthesis of glycinoeclepin A ................... 59
2.3.2 Synthesis of strigolactones ..................... 61
2.4 Other bioactive compounds of plant origin .............. 67
2.4.1 Synthesis of arnebinol .......................... 67
2.4.2 Synthesis of magnosalicin ....................... 68
2.4.3 Synthesis of hernandulcin ....................... 69
2.4.4 Synthesis of О-methyl pisiferic acid ............ 71
2.4.5 Synthesis of diospyrin .......................... 73
2.4.6 Synthesis of mispyric acid ...................... 73
References .................................................. 77
3 Synthesis of Insect Bioregulators Other than Pheromones ..... 81
3.1 Insect juvenile hormones ............................... 81
3.1.1 What are insect hormones? ....................... 81
3.1.2 Synthesis of juvabione .......................... 82
3.1.3 Synthesis of the racemates of juvenile
hormones ........................................ 86
3.1.4 Synthesis of the enantiomers of juvenile
hormones ........................................ 88
3.2 Insect antifeedants .................................... 95
3.2.1 Synthesis of polygodial ......................... 95
3.2.2 Synthesis of warburganal ........................ 97
3.2.3 Synthesis of 3,4'-dihydroxypropiophenone
3-β-D-glucopyranoside ........................... 97
3.2.4 Synthesis of homogynolide A ..................... 99
3.3 Insect repellents ..................................... 100
3.3.1 Synthesis of rotundial ......................... 100
3.3.2 Synthesis of polyzonimine ...................... 102
References ................................................. 104
4 Synthesis of Pheromones .................................... 107
4.1 What are pheromones? .................................. 107
4.2 Methods for enantioselective synthesis ................ 107
4.2.1 Derivation from enantiopure natural products ... 108
4.2.2 Enantiomer separation (optical resolution) ..... 108
4.2.3 Asymmetric synthesis ........................... 109
4.2.4 Determination of enantiomeric purity ........... 109
4.3 Why is it meaningful to synthesize enantiopure
pheromones? ........................................... 110
4.3.1 Determination of absolute configuration (1).
trogodermal .................................... 111
4.3.2 Determination of absolute configuration (2).
hemiacetal pheromone of Biprorulus bibax ....... 111
4.3.3 Determination of absolute configuration (3).
sesquiterpene pheromone of Eysarcoris lewisi ... 118
4.3.4 Clarification of the relationship between
absolute configuration and pheromone
activity-exo-brevicomin ......................... 122
4.3.5 Clarification of structure (1). lineatin ........ 124
4.3.6 Clarification of structure (2). American
cockroach pheromone ............................. 126
4.3.7 Clarification of structure (3). acoradiene ...... 129
4.3.8 Clarification of structure (4). himachalene-
type pheromone .................................. 130
4.3.9 Preparation of a pure sample for bioassay (1).
disparlure ...................................... 133
4.3.10 Preparation of a pure sample for bioassay (2).
japonilure ...................................... 137
4.3.11 Preparation of a pure sample for bioassay (3).
pheromone of the palaearctic bee, Andrena
wilkella ........................................ 139
4.4 Chiral pheromones whose single enantiomers show
bioactivity ............................................ 143
4.4.1 Dihydroactinidiolide, a pheromone component of
the red imported fire ant ....................... 143
4.4.2 Lardolure, the aggregation pheromone of the
acarid mite ..................................... 145
4.4.3 Pheromone of the fall webworm moth .............. 148
4.4.4 Posticlure, the female sex pheromone of Orgyia
postica ......................................... 151
4.4.5 Faranal, the trail pheromone of the pharaoh's
ant ............................................. 151
4.4.6 (1S,3S,7R)-3-Methyl-α-himachalene, the male
sex pheromone of the sandfly from Jacobina,
Brazil .......................................... 153
4.4.7 (S)-9-Methylgermacrene-B, the male sex
pheromone of the sandfly from Lapinha, Brazil ... 153
4.4.8 (1S,5R)-Frontalin, the bark beetle
pheromone ....................................... 153
4.4.9 (1R,5S,7R)-3,4-Dehydro-exo-brevicomin and
(S)-2-sec-butyl-4,5-dihyrothiazole, the
pheromone components of the male mouse .......... 156
4.5 Chiral pheromones whose stereochemistry-bioactivity
relationships are diverse and complicated .............. 158
4.5.1 Sulcatol, the pheromone of Gnathotrichus
sulcatus ........................................ 158
4.5.2 Sex pheromone components of female German
cockroach ....................................... 159
4.5.3 Stigmolone, the pheromone of a myxobacterium
Stigmatella aurantiaca .......................... 166
4.5.4 Ipsenol and ipsdienol, pheromones of Ips bark
beetles ......................................... 167
4.5.5 Serricornin, the cigarette beetle pheromone ..... 168
4.5.6 Stegobinone, the drugstore beetle pheromone ..... 171
4.5.7 Supellapyrone, the sex pheromone of the
brownbanded cockroach ........................... 176
4.5.8 Olean, the sex pheromone of the olive fruit
fly ............................................. 178
4.5.9 13,23-Dimethylpentatriacontane as the sex
pheromone of a tsetse fly ....................... 181
4.6 Significance of chirality in pheromone science ......... 182
References .................................................. 184
5 Synthesis of Biofunctional Molecules of Microbial
Origin ...................................................... 189
5.1 Microbial hormones ..................................... 189
5.1.1 A-factor ........................................ 189
5.1.2 Sch II and relatives, the fruiting-inducing
cerebrosides .................................... 191
5.1.3 Basidifferquinone С ............................. 195
5.1.4 Sclerosporin .................................... 196
5.1.5 Sporogen-AO 1 ................................... 197
5.1.6 Differolide ..................................... 199
5.2 Antibiotics ............................................ 201
5.2.1 Ascochlorin ..................................... 202
5.2.2 Ascofuranone .................................... 204
5.2.3 Trichostatin A .................................. 206
5.2.4 Koninginin A .................................... 207
5.2.5 Cytoxazone ...................................... 213
5.2.6 Neuchromenin .................................... 214
5.2.7 Nocardione A and В .............................. 215
5.2.8 Cytosporone E ................................... 216
5.3 Other bioactive metabolites of micro-organisms ......... 219
5.3.1 Monocerin ....................................... 219
5.3.2 Pinthunamide .................................... 219
References .................................................. 221
6 Synthesis of Marine Bioregulators, Medicinals and Related
Compounds ................................................... 223
6.1 Marine natural products of ecological importance such
as antifeedants ........................................ 223
6.1.1 Stypoldione ..................................... 223
6.1.2 meso- and (±)-Limatulone ........................ 226
6.1.3 Testudinariol A ................................. 227
6.1.4 Stellettadine A ................................. 232
6.2 Marine natural products of medicinal interest .......... 232
6.2.1 Punaglandin 4 ................................... 232
6.2.2 Bifurcarenone ................................... 235
6.2.3 Elenic acid ..................................... 238
6.2.4 Symbioramide .................................... 240
6.2.5 Penazetidine A .................................. 242
6.2.6 Penaresidin A and В ............................. 242
6.2.7 Sulfobacin А, В and flavocristamide A ........... 245
6.2.8 Plakoside A ..................................... 245
6.3 Glycosphingolipids and sphingolipids of medical
interest ............................................... 252
6.3.1 Esterified cerebroside of human and pig
epidermis ....................................... 252
6.3.2 Ceramide B, 6-hydroxylated ceramide in human
epidermis ....................................... 256
6.3.3 KRN7000, a glycosphingolipid that stimulates
natural killer T cell ........................... 258
6.3.4 Analogs of KRN7000 prepared in 2003-2006 ........ 260
6.3.5 Cyclitol, carbasugar and modified D-galactose
analogs of KRN7000: RCAI-56 and RCAI-61 ......... 262
References .................................................. 264
7 Synthetic Examination of Incorrectly Proposed Structures
of Biomolecules ............................................. 267
7.1 Origin of incorrect or obscure structures .............. 267
7.2 Structure fabrications of historical interest .......... 268
7.2.1 Kögl's auxin-a and -b, the plant-growth
promoters ....................................... 268
7.2.2 Chemical communication system of the green
flagellate, Chlamydomonas ....................... 270
7.2.3 Early fabrications of the structures of insect
pheromones ...................................... 275
7.3 Incorrect structures resulting from inappropriate use
of purification or analytical methods .................. 276
7.4 Inappropriate structural proposal caused by problems
in bioassay methods .................................... 278
7.4.1 Blattellastanoside A and B, putative
components of the aggregation pheromone of the
German cockroach ................................ 278
7.4.2 2,2,4,4-Tetramethyl-N,N-bis(2,6-
dimethylphenyl)cyclobutane-1,3-diimine as a
putative antifeedant against the cotton boll
weevil .......................................... 284
7.5 Human errors are inevitable in chemistry, too .......... 285
References .................................................. 287
8 Conclusion-Science as a Human Endeavor ...................... 289
8.1 Small molecules are also beautiful ..................... 289
8.2 Continuous efforts may bring something meaningful ...... 290
8.3 Can a scientist eventually have a hope in the
future? ................................................ 291
Acknowledgements ............................................... 291
Index .......................................................... 293
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