Richard J Sundberg- University of Virginia
Richard J Sundberg
- University of Virginia
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Publications (226)
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Two new analogs of catharanthine have been synthesized in racemic form. They differ from catharanthine in the fusion of the indole ring to the non-aromatic portion of the iboga skeleton, with the [2,3] fusion present in catharanthine being replaced by [2,1] and [3,2] fusions. The corresponding deethyl analogs were also prepared and methodological i...
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
The topic of this chapter is electrophilic substitution of indole and its derivatives. The indole ring is highly reactive
at its 3-position toward protonation, halogenation, alkylation and acylation. Electrophilic substitution can be combined with
inter- or intramolecular addition at C-2. Intramolecular alkylation by iminium ions (Pictet-Spengler r...
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
It is fair to say that the single reaction that has received the greatest attention of organic chemists is nucleophilic substitution in aliphatic systems. The reaction is of enormous synthetic utility, and a seemingly bewildering number of facts and observations had accumulated before systematic efforts at unraveling the puzzle by mechanistic studi...
Addition and elimination processes are the reverse of one another. In general, the two processes follow a similar mechanistic path in opposite directions, the final state of the system depending on the conditions. For example, hydration of alkenes and dehydration of alcohols are both familiar reactions that constitute a related addition-elimination...
Electrophilic aromatic substitution reactions are important for synthetic purposes, and they also represent one of the most thoroughly studied classes of organic reactions from a mechanistic point of view. The synthetic aspects of these reactions are discussed in Part B. The discussion here will emphasize the mechanisms of several of the most compl...
While the group I and II elements magnesium and lithium were the first metals to have a prominent role in organic synthesis, several of the transition metals are also very important. In this chapter, we will discuss reactions which are important in synthetic organic chemistry that involve transition-metal compounds and intermediates. In contrast to...
Trivalent carbocations, carbanions, and radicals are the most fundamental classes of reactive intermediates. Discussion of carbanion intermediates began in Chapter 1 and has continued in several other chapters. The focus in this chapter will be on electron-deficient
reactive intermediates. Carbocations are the most fundamental example, but carbenes...
The use of organometallic reagents in organic synthesis had its beginning around 1900 with the work of Victor Grignard, who discovered that alkyl and aryl halides reacted with magnesium metal to give homogeneous solutions. The “Grignard reagents” proved to be reactive carbon nucleophiles and have remained very useful synthetic reagents since that t...
The reactions described in this chapter include some of the most useful synthetic methods for carbon-carbon bond formation: the aldol and Claisen condensations, the Robinson
annulation, and the Wittig reaction and related olefination methods. All of these reactions begin by the addition of a carbon nucleophile to a carbonyl group. The product which...
In this chapter, we will discuss the use of boron, silicon, and tin compounds to form carbon-carbon bonds. These elements are at the boundary of the metals and nonmetals, with boron being the most and tin the least electronegative of the three. The neutral alkyl derivatives of boron have the formula R3B, whereas for silicon and tin they are R4Si an...
Most of the reactions described to this point involve polar or polarizable reactants and proceed through polar intermediates or transition states. Carbanion alkylations, nucleophilic additions to carbonyl groups, and electrophilic additions to alkenes are all examples of such reactions. The reactions to be examined in the present chapter, on the ot...
Since its original appearance in 1977, Advanced Organic Chemistry has maintained its place as the premier textbook in the field, offering broad coverage of the structure, reactivity and synthesis of organic compounds. As in the earlier editions, the text contains extensive references to both the primary and review literature and provides examples o...
Since its original appearance in 1977, Advanced Organic Chemistry has maintained its place as the premier textbook in the field, offering broad coverage of the structure, reactivity and synthesis of organic compounds. As in the earlier editions, the text contains extensive references to both the primary and review literature and provides examples o...
For Abstract see ChemInform Abstract in Full Text.
Iboga alkaloids are found in plants of the family Apocynaceae, which falls within the order Gentianales. The iboga alkaloids are examples of the broad class of monoterpenoid indole alkaloids that are considered a chemical marker for the Apocynaceae. This chapter discusses the chemistry of iboga alkaloids and their role as precursors of anti-neoplas...
To conclude this chapter, it is important to emphasize a logical point about the determination of reaction mechanisms. A proposed mechanism can never really be proven; rather, it is a case of alternative mechanisms being eliminated. Having in mind a mechanism that explains all the facts does not constitute proof that the mechanism is correct. That...
Diethyl formylmethylphosphonate served as an effective acetaldehyde synthon for synthesis of a tricyclic quinoline.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
This chapter is concerned with reactions that introduce or replace substituent groups on aromatic rings. The most important group of reactions is electrophilic aromatic substitution. The mechanism of electrophile aromatic substitution has been studied in great detail, and much information is available about structure-reactivity relationships. There...
The use of organometallic reagents in organic synthesis had its beginning around 1900 when Victor Grignard discovered that alkyl and aryl halides react with magnesium metal to give homogeneous solutions containing organomagnesium compounds. The “Grignard reagents” proved to be highly reactive carbon nucleophiles and have remained very useful synthe...
Carbon-carbon bond formation is the basis for the construction of the molecular framework of organic molecules by synthesis. One of the fundamental processes for carbon-carbon bond formation is a reaction between a nucleophilic carbon and an electrophilic one. The focus in this chapter is on enolate ions, imine anions, and enamines, which are the m...
The topic of this chapter is reduction reactions that are especially important in synthesis. Reduction can be accomplished by several broad methods, including addition of hydrogen and/or electrons to a molecule or removal of oxygen or other electronegative substituents. The most important reducing agents from a synthetic point of view are molecular...
The reactions that have been discussed in the preceding chapters provide the tools for synthesizing new and complex molecules. However, a strategy for using these tools is essential to successful synthesis of molecules by multistep synthetic sequences. The sequence of individual reactions must be planned so that they are mutually compatible. Certai...
The first two chapters dealt with formation of new carbon-carbon bonds by processes in which one carbon acts as the nucleophile and the other as the electrophile. In this chapter, we turn our attention to noncarbon nucleophiles. Nucleophilic substitution at both sp
3 and sp
2 centers is used in a variety of synthetic operations, particularly in the...
8-Methoxy-1-methyl-1H-benzo[de][1,6]naphthyridin-9-ol, isoaaptamine, a PKC inhibitor isolated from sponge was synthesized. The synthesis parallels a synthesis of 8,9-dimethoxybenzo[de][1,6]naphthyridine, aaptamine, but uses a nitromethyl substituent as a precursor of the key 5-(2-aminoethyl)-1H-quinolin-4-one intermediate. The quinolone intermediat...
A series of guanylhydrazone, amidine, and hydrazone derivatives of 2-phenylimidazo[1,2-a]pyridine have been prepared and evaluated for macrofilarial activity against Acanthocheilonema viteae and Brugia pahangi in jirds. Compounds with 4',6-bis-substitution by cyclic guanylhydrazone groups show activity. 4',6-Bis-amidines show some activity but are...
The chapter discusses the Ia cyclizations involving formation of the N-C2 bond from a preformed intermediate, which contains all the necessary atoms to construct the indole framework. The starting materials are often aromatic nitro compounds, with the cyclization taking place following reductive conversion to a nucleophilic amino group. The carbony...
This chapter discusses the structure and reactivity of pyrroles and benzo derivatives. New data was obtained on the stability of the previously uncharacterized 3H-tautomer of indole. Photodecomposition of 1 in diethyl ether generated a mixture of 3H-indole and the enol of acetophenone. 3H-indole can also be generated by photolysis of indoline in aq...
Aromatization of indolines is important in completing synthetic sequences, in which the directive effects of the indoline ring have been used to achieve selective carbocyclic substitution. One type of procedure represents use of oxidants, which are known to convert amines to imines. Aromatization then provides the indole. Such reagents must not sub...
Two routes from the oxidative cyclization product 1 derived from tyrosine to methyl 7-(tert-butyldimethylsiloxy)-N-(benzyloxycarbonyl)-2,3,7,7a-tetrahydroindole-2-carboxylate are described. The routes are stereodivergent leading to the 2-S,7-S,7a-S (6) and 2-S,7-R,7a-S-(13) diasteromers. The former stereochemistry corresponds to that present in gli...
The reactions to be described in this chapter have in common the formal involvement of even-electron intermediates having unfilled orbitals of low energy. The most familiar of these intermediates are carbonium ions. Sections 8.4 and 8.5 contain examples of fragmentation and rearrangement reactions of carbonium ions that are of synthetic value; the...
The alkylation of carbon nucleophiles by SN2-type processes is an important transformation in the synthesis of organic compounds. The generation and alkylation of such nucleophiles are described in this chapter. Alkylation and acylation of nucleophilic carbon species by other mechanisms are discussed in Chapter 2.
The unifying mechanistic pattern that appears in most of the reactions to be discussed in this chapter is a reorganization of the valence electrons of the reacting molecule or molecules. Usually, these reactions proceed through a cyclic transition state containing four, five, or six atoms. Another feature these reactions have in common is that the...
Most reductions of carbonyl and other functional groups are now done with reagents that transfer a hydride ion from a group III atom. The numerous reagents of this type that have become available provide a considerable degree of selectivity and stereochemical control. Sodium borohydride and lithium aluminum hydride are not only the most familiar ex...
Contenido: Alquilación nucleofílica de espacios entre carbonos; Reacción de carbones nucleofílicos con grupos carbonilos; Interconversión de grupos funcionales por substitución nucleofílica; Adiciones electrofílicas entre múltiples enlaces carbón-carbón; Reducción de carbonilos y otros grupos funcionales; Cicloadiciones, arreglos unimoleculares y e...
Guanylhydrazones are cationic heteroaromatic drugs similar to the diamidines which are effective in the treatment of African
trypanosomiasis and pneumocystosis. On the basis of their antitrypanosomal activity, different guanylhydrazones were selected
for evaluation in a rat model of Pneumocystis carinii pneumonia. The most active compounds were the...
The dihydropyridinium ion generated by Potier-Polonovski coupling of catharanthine and vindoline reacts with organozinc reagents to give either 15′ or 12′-substituted adducts. The former are unstable enamines but 20′-deoxyvinblastine analogs can be isolated after NaBH4 reduction. 21′-Phenylanhydrovinblastine and the 15′-ethyl, 15′-tert-butyl and 15...
Analogs of tubulin assembly inhibitors such as colchicine, combretastatin, and 3,4,5-trimethoxybiphenyl which incorporate a 6-diazo-2,4-cyclohexadienone (o-quinone diazide) ring have been synthesized and characterized. The compounds synthesized include 6-diazo-4-(2',3',4'-trimethoxyphenyl)cyclohexa-2,4-dien-1-one and its 3-methyl and 3-ethyl analog...
A series of N,N-dimethylcarbamates of 2-[(2'-, 3'-, and 4'-hydroxyphenoxy)methyl] heteroaromatic salts has been prepared. Pyridine, imidazole, quinoline, benzimidazole, and imidazo-[1,2-alpha]pyridine derivatives were included. Most of the compounds are inhibitors of electric eel acetylcholinesterase and also show prophylactic activity toward a 2LD...
A series of 2-arylimidazo[1,2-a]pyridinium salts with (N,N-dimethylcarbamoyl)oxy or (N-methylcarbamoyl)oxy groups at the 3'- or 4'-position on the phenyl substituent and various substituents on the imidazo[1,2-a]pyridine ring have been synthesized. The compounds show in vitro inhibitory activity against electric eel acetylcholinesterase (AChE), typ...
A series of quaternary heteroaromatic salts has been prepared and evaluated for prophylactic and antidotal activity towards the lethal toxicity of soman. One series of compounds contains 2-, 3-, or 4-(dimethylaminocarbonyloxy)phenoxymethyl substituents at the 2 position of the following rings: 1,3-dimethylimidazolium, 1-methylpyridinium, 1-methylqu...
Abstract— Derivatives of the tubulin polymerization inhibitors colchicine and podophyllotoxin bearing the photoreactive 2-diazo-3,3,3-trifluoropropanoyl (DTFP) group were synthesized for evaluation as potential photoaffinity labels of the tubulin binding site. All labels were assayed for their ability to inhibit tubulin polymerization, and N-DTFP-d...
The fragmentation-coupling of catharanthine and vindoline by trifluoroacetic anhydride has been carried out under conditions which allow observation of intermediates and comparison of reactivity by low temperature NMR. These studies have confirmed or revealed the following facets of the mechanism of the reaction: (1) fragmentation of an intermediat...
A group of bis-cationic imidazo[1,2-a]pyridinium salts and related compounds, some of which exhibit in vivo trypanocidal activity,
have been investigated for induction of petite mutagenesis in Saccharomyces cerevisiae. All of the compounds which are active
trypanocides induce mutagenesis. There appears to be a correlation between trypanocidal activ...
An improved reaction sequence for converting the Diels-Alder adducts of methyl α-(N- phenylsulfonylindol-2-yl)acrylate and 1-benzyloxycarbonyl-1,2-dihydropyridines to analogs of the alkaloids is described. The sequence features selective reduction of -N- methoxy-N-methylacetamide derivatives to the corresponding aldehydes followed by facile acid-ca...
Class III beta-tubulin, isolated from adult bovine brain, is resolved into at least seven charge variants on isoelectric focusing gels. To identify the posttranslational modifications responsible for this heterogeneity, a mixture of brain tubulins was treated with cyanogen bromide and the C-terminal fragments from the class III beta-tubulin isoform...
Photolysis of catharanthine in the presence of several potential electron acceptors and cyanide ion leads to either addition of cyanide at C3 and C5 or to C16-C21 fragmentation and addition of cyanide at C21. The product composition depends on the acceptor and the presence or absence of oxygen
The cyclization of 4-diazo-3-[N-(2-propenyl)amido]cyclohexadienones to cycloprop[c]indol-5-ones under the influence of copper(I) and copper(II) compounds has been investigated. Catalysis is observed with copper(I) triflate, the carbon monoxide complex of copper(I) triflate, and the carbon monoxide complexes of trifluoropentanedionato- and hexafluor...
Oxidation of catharanthine by DDQ leads to formation of products resulting from fragmentation of the C16-C21 bond as well as C3 and C5 dehydrogenation. Among the products are compounds containing a cyclopropane ring formed by bonding between C14 and C16. Cyclopropane ring formation can be also be observed from the intermediate generated by Potier-P...
The Diels-Alder adducts formed from 1-(benzyloxycarbonyl)-1,2-dihydropyridine or 1-(benzyloxycarbonyl)-4-methoxy-1,2-dihydropyridine by reaction with methyl 2-[1-(phenylsulfonyl)-1H-indol-2-yl]-2-propenoate can serve as precursors of the 5,6-homologues of the iboga alkaloid skeleton. The eight-membered C-ring can be closed by introduction of a thre...
A series of quaternary 2-phenylimidazo[1,2-a]pyridinum salts has been prepared and evaluated for antiparasitic activity. Primary attention was focused on derivatives with amido, substituted hydrazone, and heterocyclic functionality at the para position of the phenyl substituent. Guanylhydrazones and N-substituted guanylhydrazones of the 4'-formyl-s...
Organic chemistry is a broad field which intersects with such diverse areas as biology, medicine and pharmacology, polymer technology, agriculture, and petroleum engineering. At the core of organic chemistry are fundamental concepts of molecular structure and reactivity of carbon-containing compounds. The purpose of this text is to cover the centra...
The meaning of the word aromaticity has evolved as understanding of the reason for the special properties of benzene and other aromatic molecules has deepened. Originally, aromaticity was associated with a special chemical reactivity.1 The aromatic hydrocarbons were considered to be those unsaturated systems that underwent substitution reactions in...
In this section, we will discuss reactions which involve carbocation intermediates. These include carbon-carbon bond-forming reactions and also rearrangements and fragmentation reactions. The discussion will also include processes which are closely related in reactivity pattern but which avoid “free” carbocation intermediates.
