Design and Strategy in Organic Synthesis From the Chiron Approach to Catalysis

by Hanessian, Stephen; Giroux, Simon; Merner, Bradley L.

• ISBN13: 9783527319640
• ISBN10: 3527319646
• Edition: 1st
• Format: Paperback
• Copyright: 2013-09-03
• Publisher: Wiley-VCH

Summary

This long-awaited graduate level textbook adopts a refreshingly unique approach, and is written by one of the world's leading organic chemists. Following an introductory look at the concept of synthesis, the text goes on to discuss sources of enantiomerically pure compounds, the Chiron approach, locating the various substructures, synthesis with the various precursors and computer-aided synthesis. The whole is rounded off by an appendix with selected transformations of amino acids, carbohydrates, hydroxyacids and terpenes. A must-have source of first-class information for everyone working in organic synthesis, not only for graduate students.

Author Biography

Stephen Hanessian holds the Isis Pharmaceutical Research Chair at the University of Montreal and is also on the faculty of the Departments of Chemistry, Pharmaceutical Sciences and Pharmacology at the University of California, Irvine. He has received numerous awards and distinctions, the latest being the 2012 Ernest Guenther Award in the Chemistry of Natural Products from the American Chemical Society, and the IUPAC-Prize in Medicinal Chemistry.

Simon Giroux was born and raised in Montreal, Canada. He received his PhD in 2006 with Prof. Stephen Hanessian and subsequently spent 2 years in the laboratory of Prof. E. J. Corey at Harvard University, as an NSERC postdoctoral fellow. He is currently working as a medicinal chemist at Vertex Pharmaceuticals in Cambridge, Massachusetts.

Bradley L. Merner is a native of St. John?s, Newfoundland, Canada. He completed is PhD degree under the direction of Prof. Graham J. Bodwell at Memorial University working in the area of nonplanar aromatic hydrocarbon synthesis. In January of 2009, he moved to his current position as postdoctoral research associate in the laboratories of Prof. Stephen Hanessian at the University of Montreal.

Table of Contents

THE CONCEPT OF SYNTHESIS
Organic Synthesis as a Central Science
Organic Chemistry and the Public
The "Small Molecules" of Life
Nature's Rules
Organic Synthesis as a Mental and Visual Science
Art, Architecture, and Synthesis
Simplification of Complexity
Seeing Through the Mind?s Eye
Beauty is in the Eye of the Beholder
THE "WHY" OF SYNTHESIS
Nature the Provider, Healer and Enticer
The Supply Problem
From Bench to Market
Thank You Nature!
Chasing Bugs with a Purpose
Structure-Based Organic Synthesis
Almost There
The Futility of it All
Synthesis as a Seeker of Truth
Nature as the Ultimate Synthesizer
A Brave New Chemical World
Exploring New Synthetic Methods
THE "WHAT" OF ORGANIC SYNTHESIS
Periods, Trends, and Incentives
A Century of Synthesis
We the "Synthetic" People
Complex and Therapeutic too!
Peptidomimetics and Unnatural Compounds
Diversity Through Complexity
THE "HOW" OF SYNTHESIS
The Visual Dialogue
The Psychobiology of Synthesis Planning
The Agony and Ecstasy of Synthesis
Rembrandt Meets Woodward
The Post Woodwardian Era
Catalysis and Chirality in Total Synthesis
SOURCES OF ENANTIOPURE COMPOUNDS
Optical Resolution
Chemical Kinetic Resolution (KR)
Cell-Free Enzyme-Mediated Enantiopure Compounds
Cell-Free Chemoenzymatic Methods
Metal-Catalyzed Dynamic Chemical Resolution (DCR)
Biocatalytic Methods for Enantiopure Compounds
Applications of Enzymatic and Chemoenzymatic Methods
Chemical Asymmetric Synthesis of Enantiopure Compounds
Enantiopure Compounds from Nature
THE CHIRON APPROACH
Living Through a Total Synthesis
Principles of the Chiron Approach
Anatomy of a Synthesis
NATURE'S CHIRONS
Alpha-Amino Acids
Carbohydrates
Alpha-Hydroxy Acids
Terpenes
Cyclitols
FROM TARGET MOLECULE TO CHIRON
Where's Waldo?
Apparent Chirons
Partially Hidden Chirons
Hidden Chirons
Chirons as "Sacrificial Lambs"
Locating Amino Acid-Type Substructures
Locating Carbohydrate-Type Substructures
Locating Hydroxy Acid-Type Substructures
Locating Terpene-Type Substructures
Locating Carbocyclic-Type Substructures
Locating Chirons Derived from Lactones
APPLICATIONS OF THE CHIRON APPROACH
Category I Target Molecules
Category II Target Molecules
Category III Target Molecules
Prelude to Total Synthesis of Category I Molecules
TOTAL SYNTHESIS FROM AMINO ACID PRECURSORS
Actinobolin
Aspochalasin B
Cephalotaxine
Alpha-Kainic Acid
Alpha-Kainic Acid
Croomine
Biotin
Salinosporamide A
Thienamycin
FR901483
Tuberstemonine
Phyllanthine
Oscillarin
Miscellenea
TOTAL SYNTHESIS FROM CARBOHYDRATE PRECURSORS
Ajmalicine
Actinobolin
trehazolin and Trehazolamine
Fomannosin
9Alpha-Desmethoxy Mitomycin A
Saxitoxin
Decarbamoyl ent. Saxitoxin
Zaragozic Acid A
Hemibrevitoxin B
Carbohydrates in Synthesis and Biology
Miscellanea
TOTAL SYNTHESIS FROM HYDROXY ACIDS
Griseoviridin
Halicholactone
Brasilenyne
Octalactin A
(3Z)-Dactomelyne
UCS 1025A
Miscellanea
TOTAL SYNTHESIS FROM TERPENES
Picrotoxinin
Eucannabinolide
Trilobolide and Thapsivillosin
Briarellin E and F
Samanderine Y
Ambiguine H and Hapalindole U
Platensimycin
Phomactin A
Pinnaic Acid
Fusicoauritone
Miscellanea
TOTAL SYNTHESIS FROM CARBOCYCLIC PRECURSORS
Punctatin A
Acanthoic Acid
Stachybocin Spirolactam
Scabronine G
Chapecoderin A
Dragmacidin F
Reserpine
Fawcettimine
Tamiflu
Miscellanea
TOTAL SYNTHESIS FROM LACTONE PRECURSORS
Megaphone
Dihydromevinolin
Mennostatin A
Furaquinocin C
Miscellanea
SINGLE TARGET-ORIENTED SYNTHESIS
Synchronicity
Joining Forces
Back-to-Back Publishing
Same Year Publications
Single Target Molecules with Special Relevance
Quinine
Lactacystin
Taxol
MAN, MACHINE, AND VISUAL IMAGERY IN SYNTHESIS PLANNING
The LHASA Program
syngen
wodca
The CHIRON Program
Computer-Aided Synthesis Planning
THE ESSENCE OF SYNTHESIS -
A RETROSPECTIVE
Lest we Forget
The Corey and Stork Schools
The Visual Dialogue with Molecules
Total Synthesis: From whence we came
In Pursuit of the "Ideal Synthesis"
For the Love of Synthesis (Synthephilia)
Organic Synthesis: The where we are going (Quo vadis)
Synthesis at the Service of Humankind
From the Chiron Approach to Catalysis
A Salute to the Vanguards of Synthesis