Physical Sciences and Mathematics Commons^™

Efforts Towards The Asymmetric De Novo Synthesis Of Lanostanes And Euphanes, Htoo Tint Wai

Dartmouth College Ph.D Dissertations

Tetracyclic triterpenoids are ubiquitous in nature and biology, with members displaying a wide range of medically relevant properties and occupying rather distinct regions of chemical space. Members of this large class include well-known steroid hormones and sterols as well as structurally interesting subclasses such as lanostanes and euphanes, among others. Comprised of the tetracyclic skeleton with three stereodefined quaternary centers at ring-junction positions, lanostanes and euphanes present synthetic challenges that are different from those encountered in efforts targeting the structurally less complex steroid hormones. Lanostanes, in particular, stand as a historically important class of compounds as significant attention has been …

Intramolecular Friedel-Crafts Addition Of Indoles To Tertiary Allylic Alcohols, Bryan H. Wakefield, Romie Barnes, Traeannah Brown, Ashley M. Jones, Victoria A. Knotts, Christina Martinetti

Journal of the South Carolina Academy of Science

An intermolecular Friedel-Crafts alkylation of indole and tertiary allylic alcohols has been developed. The allylic alcohols were synthesized using a two-step procedure, then exposure of these alcohols to diphenyl phosphate facilitated the desired annulation reaction. This reaction tolerated a variety of indole substitutions to yield 1H,2H,3H,4H-pyrido[1,2-a]indoles.

Accessing Improbable Foldamer Shapes With Strained Macrocycles., Ko Urushibara, Yann Ferrand, Zhiwei Liu, Kosuke Katagiri, Masatoshi Kawahata, Estelle Morvan, Ryan D'Elia, Vojislava Pophristic, Aya Tanatani, Ivan Huc

Faculty Scholarship for the College of Science & Mathematics

The alkylation of some secondary amide functions with a dimethoxybenzyl (DMB) group in oligomers of 8-amino-2-quinolinecarboxylic acid destabilizes the otherwise favored helical conformations, and allows for cyclization to take place. A cyclic hexamer and a cyclic heptamer were produced in this manner. After DMB removal, X-ray crystallography and NMR show that the macrocycles adopt strained conformations that would be improbable in noncyclic species. The high helix folding propensity of the main chain is partly expressed in these conformations, but it remains frustrated by macrocyclization. Despite being homomeric, the macrocycles possess inequivalent monomer units. Experimental and computational studies highlight specific fluxional …

Synthesis Of Imidazo-1,4-Oxazinone Derivatives And Investigation Of Reaction Mechanism, Volkan Taşdemi̇r

Turkish Journal of Chemistry

In this study, nine different C-2 aroyl imidazole derivatives were synthesized in a one pot reaction with two steps, and the reduction reactions of these derivatives with NaBH4 were carried out under mild conditions. Substitution reaction of obtained imidazo methanol derivatives with chloroacetylchloride reagent and ring reaction of substitution products were investigated. It was determined that 1,4-imidazoxazinone derivative was obtained as a result of the cyclization reaction. The intermediate products obtained during the cyclization reaction were isolated, and the path of the reaction under different conditions was discussed.

Transition Metal-Free Domino Acyl Substitution/Michael Addition Of Alkenyl Grignard Reagents To Lactam Esters: Synthesis Of Lactam-Bearing Homoallylic Ketones, Abdikani Omar Farah, Muhannad Rabah, Timothy K. Beng

All Faculty Scholarship for the College of the Sciences

A solvent-controlled protocol for the direct and transition metal-free addition of alkenyl Grignard reagents to vicinally functionalized sp³-rich morpholinones has been developed, leading to the chemo and regioselective synthesis of lactam-bearing homoallylic ketones. The addition of lithium chloride proved to be essential. In cases where a new stereocenter is generated, the doubly branched homoallylic ketones are obtained in unexpectedly high diastereoselectivities. Efforts to extend the methodology to other heterosubstituted lactams revealed some important reactivity and selectivity differences.

Gama-Lactams And The Reformatsky Reaction: New Tricks For Old Chemistry, Dylan Dupont

Honors Theses

DUPONT, DYLAN. An Alternative Synthetic Pathway to γ-Lactam Compounds

Through the Application of Novel Reformatsky-Type Chemistry. Department

of Chemistry, June 2020

ADVISOR: James C. Adrian Jr. Ph.D.

It is the intent of the present report to relate the results of our attempt to elucidate and optimize a novel preparation of γ-lactam compounds. To achieve this end, it is proposed that the use of novel Reformatsky-type chemistry may provide a viable means. Generally, it has herein been validated that employment of α-amino ketones in traditional Reformatsky chemistry will form the traditional Reformatsky ester-adduct, and that this adduct is capable of spontaneously …

Stereochemical Investigation Of A Novel Tandem Intramolecular Diels-Alder Reaction, Katie Pelham

Chemistry Senior Theses

The Diels-Alder reaction has become a prominent synthetic tool due to the effectiveness for which it facilitates the construction of new carbon-carbon bonds to form six-membered rings. Since first reported in 1952, Intramolecular Diels-Alder (IMDA) reactions have been widely employed for complex synthesis, especially for natural products. Our lab was the first to report a Tandem Intramolecular Diels-Alder (TIMDA) reaction, and TIMDA reactions have similarly proved powerful in the synthesis of natural products. Predicting the absolute stereochemistry of the major products of such intramolecular reactions is complicated by the competition between steric factors imposed by the necessary distortion of the …

Cobalt-Catalyzed Aerobic Oxidative Cyclization Reactions Of Bisnucleophiles: New Methodologies And The Role Of Bisnucleophiles In O2 Activation, Jiaqi Liu

Graduate Theses, Dissertations, and Problem Reports

Over the past few decades, transition metals have found wide applications in the development of selective oxidative transformations mediated by molecular oxygen. Due to the benign nature of molecular oxygen as an oxidant and an increasing awareness of green chemistry practice, tremendous progress has been made towards the development of Cu-and Pd-catalyzed aerobic oxidation reactions. As a first-row transition metal alternative to copper, cobalt has been employed in aerobic catalytic transformations for its cost-efficiency and earth abundance; however, redox-active mediators such as benzoquinone (BQ), N-hydroxyphthalimide (NHPI) or salen-type ligands are usually required. To date, reactions mediated by Co/O₂ catalytic …

Reaction Optimization Of Pyrazinoquinoxaline Based Organic Semiconductor With Cruciform Shape, Marco Valverde Paredes, Dong-Chan Lee

LSAMP Poster Presentations

In this work, an optimum reaction condition was established to synthesize a pyrazinoquinoxaline based organic semiconductor with cruciform shape.

Design And Synthesis Of Hyaluronan:Rhamm Interaction Inhibitors, Emily Rodrigues

Electronic Thesis and Dissertation Repository

A major component of the extracellular matrix is hyaluronan, a regulator of cell migration/survival and differentiation during response-to-injury processes. The receptor for hyaluronan-mediated motility (RHAMM) binds to HA and has limited constitutive expression but is upregulated during tissue injury. Blocking HA fragment:RHAMM interactions has therapeutic potential for treating cancer but truncation of RHAMM into peptides mimicking only the HA binding domains is predicted to lose their natural α-helical structure. The goal of this project is to explore the effects cyclizing each binding domain has on helicity and its biological effect. Eighteen peptides were synthesized and cyclized using lactam bridges. The …

The Synthesis Of 1,3-Difluoro-2-Methyl-4-Phenylbenzene From A One-Pot Reaction Of Difluorocarbene And 1-Phenyl-2-Methylcyclobutene, Ruth Felicitas Menger

Senior Honors Projects, 2010-2019

Previous studies show that 1,2-disubstituted cyclobutenes can be used in reaction with difluorocarbene to produce 1,3-difluorobenzenes. A pathway to the synthesis of these types of compounds is of interest due to their presence in fluoroquinolone antibacterials, resins, and insecticides. The synthesis is unique because the fluorine atoms from the difluorocarbene are not adjacent to each other when the ring expands to a benzene ring. This study focuses on the reaction of difluorocarbene with 1-phenyl-2-methylcyclobutene, which was synthesized in one-pot in 4 steps starting from 1-phenyl-1-propyne and zirconocene dichloride.

The Effect Of Acrylic Acid On Ring Formation In Polyacrylonitrile, Elisha Cade Willis

Honors Theses

The addition of comonomers into carbon fiber precursor, polyacrylonitrile (PAN), has shown to have effects on the extent of stabilization and thermal behavior.1 Acrylic Acid (AA) was added at varying initial apparent weight percent and added via semibatch reaction to copolymerize with acrylonitrile to form carbon fiber precursor. Accompanying batch reactions were synthesized for comparison. Degradation was found to be greater in the semibatch reactions although overall was comparable to the batch reactions. Differential scanning calorimetry (DSC) confirmed the addition of higher concentrations of AA into the reaction resulted in a less intense exotherm upon cyclization, along with a greater …

Ultrasound Assisted One-Pot Synthesis Of Benzo-Fused Indole-4, 9-Dinones From 1,4-Naphthoquinone And Α-Aminoacetals, Quang H. Luu, Jorge D. Guerra, Cecilio M. Castañeda, Manuel A. Martinez, Jong Saunders, Benjamin A. Garcia, Brenda V. Gonzales, Anushritha R. Aidunuthula, Shizue Mito

Chemistry Faculty Publications and Presentations

A one-pot synthesis of benzo[f]indole-4,9-diones from 1,4-naphthoquinone with α-aminoacetals has been developed. This method provides a straightforward synthesis of benzo[f]indole-4,9-diones via intramolecular nucleophilic attack of aminoquinones to aldehydes under mild reaction conditions. The detailed mechanism was also investigated.

Direct, Biomimetic Synthesis Of (+)-Artemone Via A Stereoselective, Organocatalytic Cyclization, Eric D. Nacsa, Brian C. Fielder, Shannon P. Wetzler, Veerasak Srisuknimit, Jonathan P. Litz, Mary J. Van Vleet, Kim Quach, David A. Vosburg

All HMC Faculty Publications and Research

We present a four-step synthesis of (+)-artemone from (–)- linalool, featuring iminium organocatalysis of a doubly diastereoselective conjugate addition reaction. The strategy follows a proposed biosynthetic pathway, rapidly generates stereochemical complexity, uses no protecting groups, and minimizes redox manipulations.

Controlled Degradation Of Poly(Ester Amide)S Via Cyclization Of Pendant Functional Groups, Jose Samuel Mejia

Electronic Thesis and Dissertation Repository

Polyesters have been used for many biomedical applications ranging from sutures to drug delivery vehicles. However, their bulk degradation results in an accumulation of acidic byproducts, which is detrimental to the human body. In order to circumvent this problem, as well as to impart new properties and functions to polymers for biomedical applications, poly(ester amide)s (PEAs) have been proposed as a different class of biodegradable polymers. However, up to date, there exists no way to stimulate the degradation of these polymers.

The Gillies research group has previously incorporated self-immolative spacers into polymers and has been able to stimulate their degradation …

Studies Toward Tetrahydrofuran-Containing Natural Products: Total Synthesis Of Amphidinolide C And Oxylipids, Sudeshna Roy

Dissertations

Tetrahydrofurans (thf) and tetrahydropyrans (thp) are important structural motifs found in a broad array of biologically relevant natural products such as polyether antibiotics and acetogenins. Classic methods used for thf- or thp-ring synthesis have their own advantages and disadvantages which tend to be substrate specific. Therefore, development of new and efficient methods is imperative especially to address the issue of diastereoselectivity when attainment of both cis- and trans-2,5-thf (or 2,6-thp) is highly desirable. Herein, a strategy of cross-metathesis and Pd(0)-catalyzed cyclization, useful for obtaining both cis- and trans-2,5-disubstituted thf (or 2,6-disubstituted thp), will be discussed along with its application in …

Synthesis Of ‘Spacer’-Naproxen [2-(6-Methoxybiphenylen-2-Yl)Propanoic Acid] And -Isonaproxen [2-(7-Methoxybiphenylen-2-Yl)Propanoic Acid], Juan A. González Gómez, James R. Green, Peter C. Vollhardt

Chemistry and Biochemistry Publications

The CpCo(CO)₂-catalyzed cocyclization of 1,2-diethynyl- 4-methoxybenzene with alkynes can be applied to the synthesis of ‘spacer’-naproxen [2-(6-methoxybiphenylen-2-yl)propanoic acid] and its 7-methoxy isomer, ‘spacer’-isonaproxen. While unsymmetrical alkynes are incorporated without regioselectivity, the methoxy group in 6-methoxy-2,3-bis(trimethylsilyl)biphenylene directs electrophiles to C-3, thus allowing for regiochemical differentiation between the 2- and 3-positions.

Gram Scale Synthesis Of The C(18)-C(34) Fragment Of Amphidinolide C., Nicholas A Morra, Brian L Pagenkopf

Chemistry Publications

The synthesis of the C(18)-C(34) fragment of amphidinolide C has been achieved via two routes, culminating in both the shortest (11 steps) and highest yielding (26% overall yield) approaches to this segment. The highly convergent approach will facilitate the synthesis of analogues, including the C(18)-C(29) fragment of amphidinolide F. Synthetic highlights include the selective methylation of a diyne, and the highly efficient use of a second generation cobalt catalyst in the Mukaiyama oxidative cyclization to form the trans-THF ring.

Gram Scale Synthesis Of The C(18)-C(34) Fragment Of Amphidinolide C., Nicholas A Morra, Brian L Pagenkopf

Chemistry Publications

The synthesis of the C(18)-C(34) fragment of amphidinolide C has been achieved via two routes, culminating in both the shortest (11 steps) and highest yielding (26% overall yield) approaches to this segment. The highly convergent approach will facilitate the synthesis of analogues, including the C(18)-C(29) fragment of amphidinolide F. Synthetic highlights include the selective methylation of a diyne, and the highly efficient use of a second generation cobalt catalyst in the Mukaiyama oxidative cyclization to form the trans-THF ring.

Vinylogous Nicholas Reactions In The Synthesis Of Icetexane, Faveline, And Related Ring Systems, Izabela Kolodziej, James R. Green

Chemistry and Biochemistry Publications

The intramolecular vinylogous Nicholas reactions of aryl substituted acetoxy enyne-Co(2)(CO)(6) complexes afford tricyclic 6,7,6-ring systems and related systems in good yield.

Ytterbium Triflate Catalyzed Synthesis Of Alkoxy-Substituted Donor-Acceptor Cyclobutanes And Their Formal [4 + 2] Cycloaddition With Imines: Stereoselective Synthesis Of Piperidines., Mahmoud M Abd Rabo Moustafa, Brian L Pagenkopf

Chemistry Publications

A new synthesis of 2-alkoxy-1,1-cyclobutane diesters and their first use in dipolar cycloadditions is reported. Both the formation of the donor-acceptor cyclobutanes and their subsequent annulation with in situ formed imines are catalyzed by Yb(OTf)(3). Cyclobutanes with carbon donor groups give piperidines with high trans stereoselectivity.

Formal [4 + 2] Cycloaddition Of Alkoxy-Substituted Donor-Acceptor Cyclobutanes And Aldehydes Catalyzed By Yb(Otf)3., Mahmoud M Abd Rabo Moustafa, Andrew C Stevens, Ben P Machin, Brian L Pagenkopf

Chemistry Publications

The cycloaddition between 2-alkoxy-1,1-cyclobutane diesters and aromatic, heteroaromatic, or aliphatic aldehydes under Yb(OTf)(3) catalysis generates tetrahydropyrans in high yields with exclusive cis-stereochemistry.

Increased Yields And Simplified Purification With A Second-Generation Cobalt Catalyst For The Oxidative Formation Of Trans-Thf Rings., Cory Palmer, Nicholas A Morra, Andrew C Stevens, Barbora Bajtos, Ben P Machin, Brian L Pagenkopf

Chemistry Publications

The synthesis of a second-generation cobalt catalyst for the formation of trans-THF products via the Mukaiyama aerobic oxidative cyclization is reported. Two procedures have been developed with the new water-soluble catalyst that give superior yields and greatly simplify purification compared to the previous catalysts.

Total Synthesis Of (+/-)-Goniomitine Via A Formal Nitrile/Donor-Acceptor Cyclopropane [3 + 2] Cyclization., Christian L Morales, Brian L Pagenkopf

Chemistry Publications

The total synthesis of (+/-)-goniomitine has been accomplished in 17 linear steps with 5.2% overall yield starting from commercially available delta-valerolactam. A synthetic highlight includes the first application of a formal [3 + 2] cycloaddition between a highly functionalized nitrile and a donor-acceptor cyclopropane to prepare an indole nucleus. The use of a microwave reactor is shown to greatly improve the reaction times for two steps.

First Total Synthesis And Structural Reassignment Of (-)-Aplysiallene., Jian Wang, Brian L Pagenkopf

Chemistry Publications

The first total synthesis of (-)-aplysiallene has been completed in 16 steps and features a key sequential Mukaiyama aerobic oxidative cyclization to prepare the fused bis-THF core. The original stereochemical assignment has been revised as shown.

Synthesis And Characterization Of Some 3-Alkyl-4-Amino-5-Cyanomethyl-4h-1,2,4-Triazoles, Nesli̇han Demi̇rbaş, Ahmet Demi̇rbaş, Kemal Sancak

Turkish Journal of Chemistry

The preparation and characterization of some 3-alkyl-4-amino-5-cyanomethyl-4H-1,2,4-triazoles with active methylene groups are described and their structural properties using NMR and IR spectra and elemental analyses are given.