Make me a molecule AspirinTamiflu ® Rearrangement of atoms: cleaving and making bonds Tagamet ®

M any of the materials we use today are made by chemical synthesis. Most of the new compounds made today are organic.

Most of the new compounds made today are organic, that is, they are composed largely of carbon. Organic Chemistry Organic Compounds stable and versatileunstable

Product e.g. paint and pigment vitamin synthetic fiber pesticide plastic explosive pharmaceutical

MAKING COMPLEX MOLECULES Hermann Emil Fischer Germany ( ) Fischer achieved the first synthesis of the first truly complicated organic molecules, the sugar molecule D-glucose in The Nobel Prize in Chemistry 1902 D-Glucsoe Fischer’s work on the total synthesis of D-glucose is regarded as the catalyst for the development of synthetic organic chemistry in the 20 th century.

Sir Robert Robinson United Kingdom ( ) The Nobel Prize in Chemistry 1947 Willstatter’s synthesis of tropine Robinson’s synthesis of tropinone in 1917 The Robinson’s synthesis of tropinone was hailed as revolutionary. This was to look at the target molecule and try to imagine how the molecule could be constructed from simpler chemical units.

Robert Burns Woodward

Quinine (1944) anti-malarial drug Vitamin B12 (1973) Strychnine (1954) pesticide Some of the Complex Molecules Made by Woodward “There is excitement, adventure, and challenge, and there can be great art in organic synthesis.” - Woodward

Corey, Elias James 1928–, American organic chemist and educator, b. Methuen, Mass., grad. Massachusetts Institute of Technology (B.S. 1948, Ph.D. 1951). In 1990, he was awarded the Nobel Prize in Chemistry. Some prostaglandins affect human blood pressure at concentrations as low as 0.1 microgram per kilogram of body weight. Substances that inhibit prostaglandin synthesis may be useful in controlling pain, asthma attacks, and anaphylactic shock and in reducing the clotting ability of blood. Prostaglandins

Retrosynthetic Analysis by Corey Retrosynthetic analysis (or retrosynthesis) : the process of mentally breaking down a molecule into starting materials Retrosynthetic arrow: an open-ended arrow,, used to indicate the reverse of a synthetic reaction Synthon: idealized fragments resulting from a disconnection. Synthons need to be replaced by reagents in a suggested synthesis Retrosynthetic analysis for violet oil component Synthesis of violet oil component

Efficiency and selectivity are important characteristics that have to be taken into account. [Efficiency: yields, number of steps] [Selectivity: chemoselectivity, regioselectivity, stereoselectivity] Organic Synthesis: 1.Carbon-Carbon Bond Formation 2.Functional Group Interconversion

Organic Synthesis: 1.Carbon-Carbon Bond Formation 2.Functional Group Interconversion Stereoselectivity

Organic Synthesis: 1.Carbon-Carbon Bond Formation 2.Functional Group Interconversion Enantioselectivity

분자식 입체이성질체 (Stereoisomers) cis-1,2-dichloroethylene (bp: 60 o C) trans-1,2-dichloroethylene (bp: 48 o C) cistrans (+)-2-iodobutane (bp: 119 o C) (-)-2-iodobutane (bp: 119 o C) “ Enantiomer ” Chiral compounds

Chiral Molecules and Achiral Molecules Mirror Images identical (superimposable) identical (superimposable) enantiomers (nonsuperimposable) achiral chiral Enantiomers and the Tetrahedral Carbon

Louis Pasteur Chemist “ Chance favors only prepared mind. ” - Louis Pasteur Louis Pasteur was born on December 27, 1822 in Dole, in the region of Jura, France. Resolution of enantiomers in 1848 Twenty years later, J. H. van’t Hoff and J.-A. Le Bel independently explained the origins of enantiomers based on the tetrahedral nature of carbon bonding.

Optical Activity Light restricted to pass through a plane is plane-polarized. Solutions of chiral compounds rotate plane-polarized light and the molecules are said to be optically active.

Some Physical Properties of the Stereoisomers of Tartaric Acid

To obtain one pure enantiomer, resolution is required. Only one enantiomer is obtained by asymmetric synthesis.

Synthesis of One Enantiomer using a Chiral Auxiliary Chiral Auxiliary : [ ] Asymmetric Synthesis

The Nobel Prize in Chemistry 1979 Hebert C. Brown (1912- ) Synthesis of an Enantiomer using a Chiral Reagent Asymmetric Synthesis

Synthesis of an Enantiomer using a Chiral Catalyst Asymmetric Synthesis 92% yield, 97%ee

Synthesis of an Enantiomer using a Chiral Catalyst Asymmetric Synthesis

The anticancer drug, Taxol Synthesis: K. C. Nicolaou at The Scripps Research Institute Robert Holton at Florida State University

Acid-Base ChemistryOrganometallic Chemistry relatively stable complex unstable species stable (neutral) Carbon Species carbanionradical carbene carbocation

1. Stabilize unstable organic compounds - strained, unstable - does not exist at normal temperatures and pressures - reacts with itself to form larger ring - stable - well-behaved and easily-manipulated - readily seperated - a convenient source of cyclobutadiene

2. Change characters of organic compounds - surrounded by a cloud of negative electrons - prefer to interact with positively-charged molecules - reacts with itself to form larger ring - Cr(CO) 3 sucks away electrons from benzene - prefer to interact with negatively-charged molecules

4 4 = 256 개 tetramer Combinatorial Library 4 개의 monomer N n Combinations Combinatorial Chemistry

resin + monomer shake resin cleavage wash Solid Phase Synthesis 의 기본원리 wash

Split-Mix Process Mix-Split Couple Mix-Split Couple 3 3 = 27 tag each bead!

Solid Phase Library 20 3 = 8000 tripeptides 20 amino acids 20 2 = 400 dipeptides 20 4 = 160,000 tetrapeptides In 1991s, Houghten & Lam: synthesis of a huge peptide library peptide DNA: fully automatic (solution) Solid-phase synthesis ln 1992, Jon Ellman: synthesis of non-peptide drug-like molecules by solid phase synthesis carbohydrate small molecule (drug-like)

초분자 화학 2. Supramolecular chemistry- Chemistry beyond molecules Assembly of molecules – Molecular recognition 1987 노벨화학상 : 초분자화학 Charles Pedersen, Jean-Marie Lehn, and Donald J. Cram Non-covalent bonds: - electrostatic forces - hydrogen bonds - van der Waals interactions - dipole interactions - hydrophobic interactions, etc Supramolecular Chemistry 1. Molecular chemistry- Covalent bond

The Binding between Drug and Bilogical Receptors through Non-Covalent Bonds Biological Receptor Drug Molecule Biological Effects ‘recognition’ Supramolecular ‘complex’ physiological response

DNA Double Helix

Carcerand

Chemosensors Signals: - fluorescence - color - electric signal...