|
|
Design and Strategy in Organic Synthesis
Stephen Hanessian, Simon Giroux
|
Últimas novedades
química general
|
|
Written by the prize winner of the 2012 IUPAC-Richter and the 2012 Ernest Guenther Award!
This long-awaited graduate level book, written by one of the world’s leading organic chemists in collaboration with two of his former and present coworkers, adopts a refreshingly unique approach to synthesis planning and execution.
Following an introductory look at the concept of synthesis, the authors discuss the Why, What, and How of organic synthesis as they apply to natural products. Although emphasis is on the Chiron Approach utilizing amino-acids, carbohydrates, hydroxy acids, terpenes, lactones and other naturally occurring small molecules as starting materials, catalytic asymmetric methods are also included as a corollary whenever relevant.
A must-have source of first class information for everyone working in organic synthesis, be it in academia or industry.
|
| indíce |
Foreword XVII
Preface XIX
Acknowledgement XXIII
Abbreviations XXV
1 The Concept of Synthesis 1
1.1 Organic Synthesis as a Central Science 1
1.2 Organic Chemistry and the Public 3
1.3 The ‘‘Small Molecules’’ of life 6
1.4 Nature’s Rules 9
1.5 Organic Synthesis as a Mental and Visual Science 11
1.6 Art, Architecture, and Synthesis 12
1.7 Simplification of Complexity 13
1.8 Seeing Through the Mind’s Eye 15
1.9 Beauty is in the Eye of the Beholder 18
References 19
2 The ‘‘Why’’ of Synthesis 25
2.1 Nature the Provider, Healer, and Enticer 25
2.2 The Supply Problem 26
2.3 From Bench to Market 28
2.4 Thank you Nature! 30
2.5 Chasing Bugs with a Purpose 32
2.6 Structure-based Organic Synthesis 33
2.7 Almost There . . . or Just Arrived 34
2.8 The Futility of it All 35
2.9 Synthesis as a Seeker of the Truth 36
2.10 Nature as the Ultimate Synthesizer 42
2.11 A Brave New Chemical World 43
2.11.1 Beyond the molecule 43
2.11.2 Buckyballs and fullerenes 45
2.11.3 Dendrimers 45
2.11.4 Nanochemistry 45
2.11.5 Molecular machines 46
2.12 Exploring New Synthetic Methods 47
2.12.1 The Diels-Alder reaction 48
2.12.2 The direct aldol reaction 54
2.12.3 High impact catalytic oxidation and reduction reactions 57
2.12.4 High impact catalytic olefin-producing reactions 59
References 62
3 The ‘‘What’’ of Synthesis 73
3.1 Periods, Trends, and Incentives 73
3.2 A Century of Synthesis 74
3.3 We the ‘‘Synthesis People’’ 81
3.4 Complex and Therapeutic too! 82
3.5 Peptidomimetics and Unnatural Compounds 84
3.6 Diversity Through Complexity 89
References 90
4 The ‘‘How’’ of Synthesis 97
4.1 The Visual Dialogue 97
4.2 The Psychobiology of Synthesis Planning 98
4.2.1 ‘‘Psychosynthesis’’ 101
4.3 The Agony and Ecstasy of Synthesis 102
4.4 Rembrandt Meets Woodward 104
4.4.1 Cortisone 104
4.4.2 Strychnine 108
4.4.2.1 The Woodward Synthesis 109
4.4.2.2 The Overman synthesis 111
4.4.2.3 The Kuehne synthesis 113
4.4.2.4 The Bonjoch and Bosch synthesis 114
4.4.2.5 The Shibasaki synthesis 116
4.4.2.6 The Fukuyama synthesis 118
4.4.2.7 The Mori synthesis 119
4.4.2.8 The MacMillan synthesis 121
4.4.2.9 Strychnine syntheses: Synopsis 122
4.5 The Post Woodwardian Era 123
4.5.1 The convergent template-based approach 123
4.5.2 Chiral auxiliary approach 125
4.5.3 Substrate control approach in cycloadditions 127
4.5.4 Biomimetic cyclization approach 129
4.6 Catalysis and Chirality in Total Synthesis 131
4.6.1 Applications of asymmetric catalysis to drug discovery 136
References 139
5 Sources of Enantiopure Compounds 145
5.1 Optical Resolution 146
5.2 Chemical Kinetic Resolution (KR) 147
5.2.1 Classical, natural, and parallel methods 147
5.2.2 Dynamic chemical kinetic resolution 147
5.3 Cell-free Enzyme-mediated Enantiopure Compounds 149
5.3.1 Hydrolases and ester formation 149
5.3.2 Nitrilases, amidases, and acylases 152
5.4 Cell-free Chemoenzymatic Methods 154
5.5 Metal-catalyzed Dynamic Kinetic Resolution (DKR) 154
5.6 Biocatalytic Methods for Enantiopure Compounds 155
5.6.1 Enzymatic reduction of ketones 155
5.6.2 Enzymatic hydroxylation and epoxidation 156
5.6.3 Enzymatic oxidation of alcohols 157
5.6.4 Enzymatic Baeyer-Villiger oxidation 157
5.7 Applications of Enzymatic and Chemoenzymatic Methods 158
5.8 Chemical Asymmetric Synthesis of Enantiopure Compounds 160
5.9 Enantiopure Compounds from Nature 164
References 165
6 The Chiron Approach 171
6.1 Living Through a Total Synthesis 171
6.2 Principles of the Chiron Approach 172
6.2.1 Definition 173
6.2.2 The Chiron Approach 175
6.2.3 Two philosophies, one goal 176
6.2.4 There is more than meets the eye 180
6.2.5 The flipside of molecules 183
6.2.6 Common root, different MO: chirons and synthons 184
6.2.7 To chiron or not to chiron 186
6.3 Anatomy of a Synthesis 186
References 189
7 Nature’s Chirons 193
7.1 a-Amino Acids 193
7.2 Carbohydrates 195
7.3 a-Hydroxy Acids 200
7.4 Terpenes 203
7.5 Cyclitols 206
References 208
8 From Target Molecule to Chiron 213
8.1 Where’s Waldo? 214
8.2 Apparent Chirons 217
8.3 Partially Hidden Chirons 220
8.4 Hidden Chirons 222
8.5 Chirons as ‘‘Sacrificial Lambs’’ 224
8.6 Locating a-Amino Acid-type Substructures 228
8.6.1 Apparent amino acids 229
8.6.2 Partially hidden amino acids 231
8.6.3 Hidden amino acids 232
8.7 Locating Carbohydrate-type Substructures 234
8.7.1 Patterns and shapes 235
8.7.2 The ‘‘Rule of Five’’ 236
8.7.3 Apparent carbohydrates 237
8.7.4 Partially hidden carbohydrates 239
8.7.5 Hidden carbohydrates 240
8.8 Locating Hydroxy Acid-type Substructures 243
8.8.1 Apparent hydroxy acids 243
8.8.2 Partially hidden hydroxy acids 245
8.8.3 Hidden hydroxy acids 248
8.8.4 The Roche acid - a unique C-Methyl chiron 251
8.9 Locating Terpene-type Substructures 254
8.9.1 Apparent terpenes 254
8.9.2 Partially hidden terpenes 258
8.9.3 Hidden terpenes 260
8.9.3.1 The terpene route to taxol 267
8.10 Locating Carbocyclic-type Substructures 270
8.10.1 Apparent carbocycles 271
8.10.2 Partially hidden carbocycles 272
8.10.3 Hidden carbocycles 275
8.10.4 Quinic acid, cyclitols, and other carbocycles as chirons 279
8.11 Locating Chirons Derived from Lactones 283
8.11.1 Apparent lactones 285
8.11.2 Partially hidden lactones 286
8.11.3 Hidden lactones 288
8.11.4 The replicating lactone strategy 292
References 294
9 Applications of the Chiron Approach 301
9.1 Category I Target Molecules 301
9.1.1 Streptolic acid 302
9.1.2 ent-Gelsedine 303
9.1.3 Vincamine 305
9.1.4 Peribysin E 307
9.2 Category II Target Molecules 308
9.2.1 FK-506 309
9.2.2 Okadaic acid 310
9.2.3 Phorboxazole A 312
9.2.4 Brevetoxin B 314
9.3 Category III Target Molecules 316
9.3.1 Neocarzinostatin 317
9.3.2 Idiospermuline 317
9.4 Prelude to Total Synthesis of Category I Molecules 320
References 320
10 Total Synthesis from a-Amino Acid Precursors 323
10.1 Actinobolin 323
10.2 Aspochalasin B 326
10.3 Cephalotaxine 329
10.4 a-Kainic Acid (W. Oppolzer) 332
10.5 a-Kainic Acid (P. T. Gallagher) 334
10.6 Croomine 336
10.7 Biotin 339
10.8 Salinosporamide A 342
10.9 Thienamycin 345
10.10 FR901483 348
10.10.1 The Sorensen synthesis 350
10.11 Tuberostemonine 353
10.12 Phyllanthine 358
10.13 Oscillarin 361
10.14 ent-Cyclizidine 364
10.15 Pactamycin 367
10.16 Miscellanea 371
References 373
11 Total Synthesis from Carbohydrate Precursors 377
11.1 Ajmalicine 377
11.2 ent-Actinobolin 381
11.3 Trehazolin and Trehazolamine 384
11.4 Fomannosin 390
11.5 9a-Desmethoxy Mitomycin A 394
11.6 Saxitoxin and ß-Saxitoxinol 398
11.6.1 Second generation synthesis 400
11.7 ent-Decarbamoyl Saxitoxin 402
11.8 Zaragozic acid A 405
11.9 Hemibrevetoxin B 408
11.10 Carbohydrates in Synthesis and in Biology 416
11.11 Miscellanea 417
References 422
12 Total Synthesis from Hydroxy Acids 427
12.1 Griseoviridin 427
12.2 Halicholactone 431
12.3 Brasilenyne 435
12.4 Octalactin A 438
12.5 (3Z)-Dactomelyne 442
12.6 UCS1025A 446
12.7 Jerangolid A 449
12.8 Miscellanea 453
References 456
13 Total Synthesis from Terpenes 459
13.1 Picrotoxinin 459
13.2 Eucannabinolide 463
13.3 Trilobolide and Thapsivillosin F 467
13.4 Briarellin E and F 472
13.5 Samaderine Y 477
13.6 Ambiguine H and Hapalindole U 481
13.7 Platensimycin 484
13.7.1 The Nicolaou synthesis 485
13.7.2 The Ghosh synthesis 488
13.7.3 Nicolaou’s two asymmetric syntheses 491
13.7.4 Yamamoto’s organocatalytic asymmetric synthesis 494
13.7.5 Corey’s catalytic enantioselective synthesis 496
13.7.6 Platensimycin and the mind’s eye 496
13.8 Phomactin A 500
13.9 Pinnaic Acid 503
13.9.1 The Danishefsky and Zhao asymmetric syntheses 507
13.10 Fusicoauritone 510
13.11 Miscellanea 514
References 516
14 Total Synthesis from Carbocyclic Precursors 521
14.1 Punctatin A 521
14.2 Acanthoic Acid 524
14.3 Stachybocin Spirolactam 527
14.4 Scabronine G 529
14.5 Chapecoderin A 533
14.6 Dragmacidin F 533
14.7 Reserpine 538
14.7.1 The Woodward synthesis 539
14.7.2 The Stork synthesis 542
14.7.3 The Hanessian synthesis 545
14.8 Fawcettimine 548
14.8.1 Toste’s synthesis of fawcettimine 548
14.8.2 Heathcock’s synthesis of (±)-fawcettimine 551
14.9 Tamiflu 553
14.9.1 The Fang and Wong synthesis 553
14.9.2 The Hudlicky and Banwell syntheses 555
14.9.3 The Shibasaki catalytic asymmetric Diels-Alder synthesis 557
14.9.4 Tamiflu synthesis in the age of catalysis: Synopsis 558
14.10 Miscellanea 560
References 563
15 Total Synthesis with Lactones as Precursors 567
15.1 Megaphone 567
15.2 Dihydromevinolin 569
15.3 Mannostatin A 572
15.4 Furaquinocin C 577
15.5 Miscellanea 577
References 580
16 Single Target Molecule-oriented Synthesis 583
16.1 Synchronicity 583
16.2 Joining Forces 584
16.3 Back-to-back Publishing 586
16.3.1 Veratramine (1967) 587
16.3.2 (±)-Lycopodine (1968) 588
16.3.3 Ionomycin (1990) 589
16.3.4 Vancomycin aglycone (1998) 591
16.4 Same Year Publications 593
16.4.1 (±)-Colchicine (1959) 594
16.4.2 (±)-Catharanthine (1970) 595
16.4.3 (±)-Cephalotaxine (1972) 596
16.4.4 Bleomycin A2 (1982) 597
16.4.5 Kopsinine (1985) 598
16.4.6 Rapamycin (1993) 600
16.4.7 Phomoidrides (CP molecules) (2000) 604
16.4.7.1 The Nicolaou Synthesis 604
16.4.7.2 The Shair synthesis 606
16.4.7.3 The Fukuyama synthesis 608
16.4.7.4 The Danishefsky synthesis 609
16.4.7.5 What is in a drawing? 611
16.4.8 Borrelidin (2003–2004) 612
16.4.8.1 The Morken synthesis 612
16.4.8.2 The Hanessian synthesis 614
16.4.8.3 The O˜mura and Theodorakis syntheses 615
16.4.9 Amphidinolide E (2006) 618
16.5 Single Target Molecules with Special Relevance 620
16.6 Quinine 621
16.6.1 The Stork synthesis 621
16.6.2 Quinine: The Woodward and Doering formal vs total syntheses issue 624
16.6.3 Quinine: Apr´es Woodward and Doering 627
16.6.3.1 The Uskokovi´c synthesis 627
16.6.3.2 The Gates synthesis 630
16.6.3.3 The Taylor and Martin synthesis 631
16.6.4 Quinine: Total synthesis in the modern age of catalysis 631
16.6.4.1 The Jacobsen synthesis 631
16.6.4.2 The Kobayashi synthesis 633
16.6.4.3 The Williams and Krische syntheses of 7-hydroxyquinine 635
16.6.5 The total synthesis of quinine in the mind’s eye 637
16.7 Lactacystin 641
16.7.1 The first Corey synthesis 642
16.7.2 The second Corey synthesis 643
16.7.3 The Baldwin synthesis 645
16.7.4 The Chida Synthesis 647
16.7.5 The O˜mura-Smith synthesis 648
16.7.6 The Panek synthesis 650
16.7.7 The Jacobsen synthesis 651
16.7.8 The Shibasaki synthesis 654
16.7.9 Lactacystin and omuralide: Alternative methods and synthetic approaches 656
16.7.10 The Kang approach 656
16.7.11 The Adams synthesis of omuralide 657
16.7.12 The Ohfune approach 658
16.7.13 The Pattenden approach 659
16.7.14 The Hatekayama approach 659
16.7.15 The Donohue synthesis of (±)-omuralide 660
16.7.16 The Wardrop approach 661
16.7.17 The Hayes synthesis of lactacystin 662
16.7.18 Total synthesis of lactacystin: Synopsis 663
16.8 Taxol 665
16.8.1 What mad pursuit 666
16.8.2 The Holton synthesis of taxol 666
16.8.3 The Nicolaou synthesis of taxol 670
16.8.4 The Danishefsky synthesis of taxol 673
16.8.5 The Wender synthesis of taxol 676
16.8.6 The Kuwajima synthesis of taxol 679
16.8.7 The Mukaiyama synthesis of taxol 682
16.8.8 The six total syntheses of taxol: The calm after the storm 685
16.8.9 Total syntheses of taxol in the mind’s eye 686
References 690
17 Man, Machine, and Visual Imagery in Synthesis Planning 699
17.1 The LHASA Program 701
17.2 SYNGEN 702
17.3 WODCA 703
17.4 The CHIRON Program 704
17.4.1 CASA (Computer-assisted stereochemical analysis) 704
17.4.2 CAPS (Computer-assisted precursor selection) 705
17.5 Computer-aided synthesis planning 710
References 711
18 The Essence of Synthesis – A Retrospective 713
18.1 Lest we Forget 714
18.2 The Corey and Stork Schools 714
18.3 The Visual Dialogue with Molecules 716
18.4 Total Synthesis: From whence we came. . . 717
18.5 In Pursuit of the ‘‘Ideal Synthesis’’ 722
18.5.1 The problem with protecting groups – blessing or curse? 724
18.5.1.1 Protecting-group-free synthesis? 725
18.5.2 The ‘‘redox economy’’ problem 725
18.5.3 The ‘‘functional group adjustment’’ problem 726
18.5.4 ‘‘Chiral economy’’ 727
18.6 For the Love of Synthesis (Synthephilia) 730
18.6.1 Reaching the summit 731
18.7 Organic Synthesis: To where we are going 732
18.8 Synthesis at the Service of Humankind 734
18.9 From the Chiron Approach to Catalysis 736
18.9.1 The young, the brave, and the bold: Passing the baton 740
18.9.1.1 Himandrine 740
18.9.1.2 Palau’amine 743
18.9.1.3 Minfiensine 745
18.9.1.4 Maoecrystal Z 747
18.9.2 Parting thoughts 749
18.10 A Salute to the Vanguards of Synthesis 749
References 750
Author Index [Natural product/Target] 757
Chiron/Starting Material to Natural Product/Target Index 771
Natural product/Target [Chiron] 781
Key (Named) Reactions Index 791
|
|
|