Larry E. Overman
Encyclopedia
Larry E. Overman is Distinguished Professor of Chemistry at the University of California, Irvine
. He was born in Chicago in 1943. Overman obtained a B.A. degree from Earlham College
in 1965. and he completed his Ph.D. in chemistry from the University of Wisconsin–Madison
in 1969, under Howard Whitlock, Jr.. Professor Overman is a member of the United States National Academy of Sciences
and the American Academy of Arts and Sciences
. He was the recipient of the Arthur C. Cope Award
in 2003, and he was awarded the Tetrahedron Prize for Creativity in Organic Chemistry for 2008.
Overman's research is focused on the development of new chemical reactions, particularly transition metal
catalyzed
reactions, and the application of those reactions toward the synthesis
of natural product
s. Overman is most known for the Overman rearrangement
, a Claisen rearrangement
of allyl
ic alcohol
s to give allylic trichloroacetamides.
from squalene oxide via lanosterol synthase
. Overman has explained that this work gave him a lifelong love of rearrangement reaction
s. This was followed by two years as a postdoctoral fellow at Columbia University
with Ronald Breslow
, using non-covalent binding of cyclodextrin
as a model of enzyme binding.
Larry Overman began his career at University of California, Irvine in June 1971. The Irvine graduate program was small and thus in his early work Overman frequently performed experiments himself, including his initial discovery of the Overman rearrangement.
Palladium emerged as the metal of choice for this reaction, and this led to a long-term interest in palladium catalysis, including the palladium(II)-catalyzed Cope rearrangement
, and later work on intramolecular cascading Heck reaction
s.
Overman has performed many total syntheses of natural products, beginning with (±)-pumiliotoxin C
(with Peter Jessup) in the late seventies. This interest was spurred on by a 1977 sabbatical visit by Samuel J. Danishefsky
.
Overman has also worked extensively on the aza-Cope-Mannich reaction, originally designed to solve a stereoelectronic problem in the total synthesis of gephyrotoxin
.
This reaction is described by Overman as "robust", and was subsequently used in the total syntheses of several natural products, for example (–)-strychnine
. A ring-enlarging version of the reaction was used in the synthesis of secondary metabolites such as actinophyllic acid. A related reaction, a Prins
-Pinacol
cascade which produces a tetrahydrofuran
, has also been used extensively by the Overman group, for example in the total synthesis of (–)-magellanine
, a Lycopodium
alkaloid
.
University of California, Irvine
The University of California, Irvine , founded in 1965, is one of the ten campuses of the University of California, located in Irvine, California, USA...
. He was born in Chicago in 1943. Overman obtained a B.A. degree from Earlham College
Earlham College
Earlham College is a liberal arts college in Richmond, Indiana. It was founded in 1847 by Quakers and has approximately 1,200 students.The president is John David Dawson...
in 1965. and he completed his Ph.D. in chemistry from the University of Wisconsin–Madison
University of Wisconsin–Madison
The University of Wisconsin–Madison is a public research university located in Madison, Wisconsin, United States. Founded in 1848, UW–Madison is the flagship campus of the University of Wisconsin System. It became a land-grant institution in 1866...
in 1969, under Howard Whitlock, Jr.. Professor Overman is a member of the United States National Academy of Sciences
United States National Academy of Sciences
The National Academy of Sciences is a corporation in the United States whose members serve pro bono as "advisers to the nation on science, engineering, and medicine." As a national academy, new members of the organization are elected annually by current members, based on their distinguished and...
and the American Academy of Arts and Sciences
American Academy of Arts and Sciences
The American Academy of Arts and Sciences is an independent policy research center that conducts multidisciplinary studies of complex and emerging problems. The Academy’s elected members are leaders in the academic disciplines, the arts, business, and public affairs.James Bowdoin, John Adams, and...
. He was the recipient of the Arthur C. Cope Award
Arthur C. Cope Award
The Arthur C. Cope Award is a prize awarded for achievement in the field of organic chemistry research. It is generally considered one of the highest honors in the field. It is sponsored by the Arthur C. Cope Fund, and has been awarded since 1973 by the American Chemical Society.Recipients...
in 2003, and he was awarded the Tetrahedron Prize for Creativity in Organic Chemistry for 2008.
Overman's research is focused on the development of new chemical reactions, particularly transition metal
Transition metal
The term transition metal has two possible meanings:*The IUPAC definition states that a transition metal is "an element whose atom has an incomplete d sub-shell, or which can give rise to cations with an incomplete d sub-shell." Group 12 elements are not transition metals in this definition.*Some...
catalyzed
Catalysis
Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....
reactions, and the application of those reactions toward the synthesis
Organic synthesis
Organic synthesis is a special branch of chemical synthesis and is concerned with the construction of organic compounds via organic reactions. Organic molecules can often contain a higher level of complexity compared to purely inorganic compounds, so the synthesis of organic compounds has...
of natural product
Natural product
A natural product is a chemical compound or substance produced by a living organism - found in nature that usually has a pharmacological or biological activity for use in pharmaceutical drug discovery and drug design...
s. Overman is most known for the Overman rearrangement
Overman rearrangement
The Overman rearrangement is a chemical reaction that can be described as a Claisen rearrangement of allylic alcohols to give allylic trichloroacetamides through an imidate intermediate. The Overman rearrangement was discovered in 1974 by Larry Overman....
, a Claisen rearrangement
Claisen rearrangement
The Claisen rearrangement is a powerful carbon-carbon bond-forming chemical reaction discovered by Rainer Ludwig Claisen...
of allyl
Allyl
An allyl group is a substituent with the structural formula H2C=CH-CH2R, where R is the connection to the rest of the molecule. It is made up of a methylene , attached to a vinyl group . The name is derived from the Latin word for garlic, Allium sativum. Theodor Wertheim isolated an allyl...
ic alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
s to give allylic trichloroacetamides.
Career
Overman's Ph.D. focused on the mechanism of rearrangements related to the biosynthesis of lanosterolLanosterol
Lanosterol is a tetracyclic triterpenoid, which is the compound from which all steroids are derived.-Role in creation of steroids:Elaboration of lanosterol under enzyme catalysis leads to the core structure of steroids. 14-Demethylation of lanosterol by CYP51 eventually yields...
from squalene oxide via lanosterol synthase
Lanosterol synthase
Lanosterol synthase is an oxidosqualene cyclase enzyme that converts -2,3-oxidosqualene to a protosterol cation and finally to lanosterol. Lanosterol is a key four-ringed intermediate in cholesterol biosynthesis...
. Overman has explained that this work gave him a lifelong love of rearrangement reaction
Rearrangement reaction
A rearrangement reaction is a broad class of organic reactions where the carbon skeleton of a molecule is rearranged to give a structural isomer of the original molecule. Often a substituent moves from one atom to another atom in the same molecule...
s. This was followed by two years as a postdoctoral fellow at Columbia University
Columbia University
Columbia University in the City of New York is a private, Ivy League university in Manhattan, New York City. Columbia is the oldest institution of higher learning in the state of New York, the fifth oldest in the United States, and one of the country's nine Colonial Colleges founded before the...
with Ronald Breslow
Ronald Breslow
Ronald C. D. Breslow is an American chemist from Rahway, New Jersey. He is currently University Professor at Columbia University, where he is based in the Department of Chemistry and affiliated with the Departments of Biological Sciences and Pharmacology; he has also been on the faculty of its...
, using non-covalent binding of cyclodextrin
Cyclodextrin
Cyclodextrins are a family of compounds made up of sugar molecules bound together in a ring ....
as a model of enzyme binding.
Larry Overman began his career at University of California, Irvine in June 1971. The Irvine graduate program was small and thus in his early work Overman frequently performed experiments himself, including his initial discovery of the Overman rearrangement.
Palladium emerged as the metal of choice for this reaction, and this led to a long-term interest in palladium catalysis, including the palladium(II)-catalyzed Cope rearrangement
Cope rearrangement
The Cope rearrangement is an extensively studied organic reaction involving the [3,3]-sigmatropic rearrangement of 1,5-dienes. It was developed by Arthur C. Cope...
, and later work on intramolecular cascading Heck reaction
Heck reaction
The Heck reaction is the chemical reaction of an unsaturated halide with an alkene and a base and palladium catalyst to form a substituted alkene. Together with the other palladium-catalyzed cross-coupling reactions, this reaction is of great importance, as it allows one to do substitution...
s.
Overman has performed many total syntheses of natural products, beginning with (±)-pumiliotoxin C
Pumiliotoxin
Pumiliotoxins , are one of several toxins found in the skin of poison dart frogs. Closely related, though more toxic, are allopumiliotoxins, . Other toxins found in the skin of poison frogs include decahydroquinolines , izidines, coccinellines, and spiropyrrolizidines. Pumiliotoxins are very...
(with Peter Jessup) in the late seventies. This interest was spurred on by a 1977 sabbatical visit by Samuel J. Danishefsky
Samuel J. Danishefsky
Samuel J. Danishefsky is an American chemist working as a professor at both Columbia University and the Memorial Sloan-Kettering Cancer Center in New York City.- Birth and education :...
.
Overman has also worked extensively on the aza-Cope-Mannich reaction, originally designed to solve a stereoelectronic problem in the total synthesis of gephyrotoxin
Gephyrotoxin
Gephyrotoxin is a naturally occurring product that stems from the Colombian tropical frog Dendrobates histrionicus. It is a member of the class of compounds known as histrionicotoxins. This alkaloid skin secretion was first isolated from the tropical frog in 1977 by Daly and his fellow...
.
This reaction is described by Overman as "robust", and was subsequently used in the total syntheses of several natural products, for example (–)-strychnine
Strychnine
Strychnine is a highly toxic , colorless crystalline alkaloid used as a pesticide, particularly for killing small vertebrates such as birds and rodents. Strychnine causes muscular convulsions and eventually death through asphyxia or sheer exhaustion...
. A ring-enlarging version of the reaction was used in the synthesis of secondary metabolites such as actinophyllic acid. A related reaction, a Prins
Prins reaction
The Prins reaction is an organic reaction consisting of an electrophilic addition of an aldehyde or ketone to an alkene or alkyne followed by capture of a nucleophile. The outcome of the reaction depends on reaction conditions . With water and a protic acid such as sulfuric acid as the reaction...
-Pinacol
Pinacol rearrangement
The pinacol rearrangement or pinacol-pinacolone rearrangement is a method for converting a 1,2-diol to a carbonyl compound in organic chemistry. This 1,2-rearrangement takes place under acidic conditions...
cascade which produces a tetrahydrofuran
Tetrahydrofuran
Tetrahydrofuran is a colorless, water-miscible organic liquid with low viscosity at standard temperature and pressure. This heterocyclic compound has the chemical formula 4O. As one of the most polar ethers with a wide liquid range, it is a useful solvent. Its main use, however, is as a precursor...
, has also been used extensively by the Overman group, for example in the total synthesis of (–)-magellanine
Magellanine
-Magellanine is a member of the Lycopodium alkaloid class of natural products. It was isolated from the club moss Lycopodium magellanicum in 1976. It has been synthesized five times, with the first synthesis having been completed by the Larry E. Overman group at the University of California,...
, a Lycopodium
Lycopodium
Lycopodium is a genus of clubmosses, also known as ground pines or creeping cedar, in the family Lycopodiaceae, a family of fern-allies...
alkaloid
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
.
Awards
- Myron L. BenderMyron L. BenderMyron Lee Bender was born in St. Louis, Missouri. He obtained his B.S. and his Ph.D. from Purdue University. The latter was under the direction of Henry B. Hass. After postdoctoral research under Paul D. Barlett , and Frank H. Westheimer , he spent one year as a faculty member at the...
and Muriel S. Bender Summer Lectureship, Northwestern UniversityNorthwestern UniversityNorthwestern University is a private research university in Evanston and Chicago, Illinois, USA. Northwestern has eleven undergraduate, graduate, and professional schools offering 124 undergraduate degrees and 145 graduate and professional degrees....
(1994) - Arthur C. Cope AwardArthur C. Cope AwardThe Arthur C. Cope Award is a prize awarded for achievement in the field of organic chemistry research. It is generally considered one of the highest honors in the field. It is sponsored by the Arthur C. Cope Fund, and has been awarded since 1973 by the American Chemical Society.Recipients...
, 2003 - Tetrahedron Prize for Creativity in Organic Chemistry, 2008