Browsing by Author "Kurti, Laszlo"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Amination and hydroxylation of arylmetal compounds
    (2019-12-03) Gao, Hongyin; Zhou, Zhe; Kurti, Laszlo; Rice University; United States Patent and Trademark Office
    In one aspect, the present disclosure provides methods of preparing a primary or secondary amine and hydroxylated aromatic compounds. In some embodiments, the aromatic compound may be unsubstituted, substituted, or contain one or more heteroatoms within the rings of the aromatic compound. The methods described herein may be carried out without the need for transition metal catalysts or harsh reaction conditions.
  • Thumbnail Image
    Item
    Development of New Methods for the Synthesis of Novel Biaryls
    (2016-12-13) Keene, Craig Allen; Kurti, Laszlo
    Herein the first organocatalytic atroposelective synthesis of BINAM derivatives is detailed. The findings of which inspired the development of new methodology directed toward the synthesis of 3-substituted-2-nitronaphthalene building blocks. The nitronaphthalenes were then utilized in a new approach aimed at the synthesis of symmetrical and unsymmetrical diaryl hydrazines. A novel approach for the synthesis of functionalized, non-C2-symmetric, atropisomeric biaryls in a one-pot transformation is also described.
  • Thumbnail Image
    Item
    New Strategies for the Synthesis of Amines, Ethers and Small Strained Rings
    (2021-08-12) Behnke, Nicole Erin; Kurti, Laszlo
    Amines, ethers and small strained rings are ubiquitous structural motifs in biologically active compounds and consumer products. The motivation for this work was to develop operationally simple and efficient strategies for the formation C–N, C–O, and C–C bonds in structurally diverse molecules. Chapter 1 describes the development of two novel methods for the synthesis of primary aromatic and aliphatic amines via the electrophilic amination of the corresponding organometallic reagents. The key advance in these transformations is the application of sterically hindered NH-oxaziridines as chemoselective aminating reagents. The first method involves the transmetalation of aryl Grignard, organolithium, or organozinc reagents to the corresponding organocopper species and subsequent reaction with a di-tert-butyl NH-oxaziridine. The use of less basic organocopper reagents expands the substrate scope to incorporate electron-deficient and heterocyclic aryl rings as well as sensitive electrophilic functional groups in the desired primary amine products. The second method is an extension of the oxaziridine N-transfer chemistry that includes aliphatic organometallic reagents. The developed route is applied to sterically and electronically diverse primary, secondary, and tertiary alkyl Grignard and organozinc reagents to form the corresponding primary amines in good yields. Chapter 2 outlines the work conducted for the copper-catalyzed synthesis of sterically hindered ethers from -bromo carbonyl compounds. Coupling of an -bromocarboxamide or an -bromocarboxylic acid is successful with a wide variety of phenols in addition to primary, secondary, or tertiary alcohols under mild conditions. To showcase potential applications of the ether-forming method in medicinal chemistry, a mild route that improves upon literature precedent is designed and applied to the synthesis of a novel PAR-1 antagonist analogue. Chapter 3 describes advances made in the synthesis of spirocyclic NH-azetidine rings through a Ti(IV)-mediated Kulinkovich-type coupling of oxime ethers with primary alkyl Grignard reagents or terminal olefins. A significant development in this project is related to the purification and handling of the sensitive and basic NH-azetidine compounds. Oxime ether coupling with structurally and electronically diverse primary Grignard reagents evaluates the scope of NH-azetidine products while coupling with terminal olefins validates the proposed Kulinkovich-type reaction mechanism. Finally, Chapter 4 outlines another project dedicated to the synthesis of small, strained rings. A combination of three synthetic steps is used for the formation of highly substituted cyclopropane rings. First, the formation of alpha,alpha-dichlorocyclobutanone rings proceeds via a [2+2] Staudinger ketene cycloaddition from cis- or terminal olefins. Next, a complete optimization study for the generation of alpha,alpha-dichlorocyclobutanols via 1,2-addition of organocerium reagents is described. Last, a base-mediated quasi-Favorskii reaction induces a ring-contraction of the alpha,alpha-dichlorocyclobutanol ring under mild reaction conditions to the corresponding highly substituted cyclopropane product. Overall, these five methods significantly contribute to advancements in the synthesis of compounds containing amine, ether or strained ring functional groups. In addition to studying innovative reactivity patterns, a wide variety of novel compounds with structurally and electronically diverse properties are characterized.
  • Thumbnail Image
    Item
    Preparation of Secondary Amines with Electrophilic N-Linchpin Reagents
    (2023-09-26) Kattamuri, Padmanabha Venkatesh; Kurti, Laszlo; William Marsh Rice University; United States Patent and Trademark Office
    In one aspect, the present disclosure provides methods of preparing a secondary amine. In some embodiments, the secondary amine comprises two different groups or two identical groups. Also provided herein are compositions for use in the preparation of the secondary amine.
  • Thumbnail Image
    Item
    Total synthesis of shishijimicin A, design, synthesis and biological evaluation of analogues thereof, and total synthesis and full structural elucidation of namenamicin
    (2018-08-31) Li, Ruofan; Nicolaou, Kyriacos C.; Kurti, Laszlo; Farach-Carson, Mary C.
    Enediyne natural products possessing both sophisticated chemical structures and outstanding bioactivities have received intensive attentions from chemical and biological communities since their first discovery made in 1960s. The isolations of these unusual naturally occurring substances have provoked tremendous efforts from interdisciplinary areas, culminating in comprehensive understandings and implementations on fermentative production, cytotoxicity, structural elucidation, mechanism of action, biosynthesis and total synthesis. Shishijimicins A–C and namenamicin are recently discovered marine-originated 10-membered ring enediyne natural products that render subnanomolar to picomolar levels of antibacterial and antitumor potencies. While these properties are highly desired in the targeted cancer therapies, such pharmaceutical applications are largely hampered by their scarce natural sources, which led to hitherto very limited understandings on these enediyne siblings. As a counterpart to the natural producer, chemical synthesis has long been valued for its potential of providing not only naturally existing materials, but also structurally modified analogues thereof, the latter being essential for the structure–activity relationship (SAR) studies. Therefore, in Chapter 1, we disclosed our first total synthesis of shishijimicin A, featuring a practical and scalable construction of its disaccharide domain by employing glycal glycosidation, β-carboline C–H functionalization, and lithio-β-carboline–aldehyde coupling reactions. The established synthetic methods and strategies have enabled the generation of an array of shishijimicin A analogues with various degree of chemical modifications as described in Chapter 2. The biological evaluations of the latter revealed several tolerable and intolerable structural changes with regards to the cytotoxic potencies, resulting in a graphic SAR on shishijimicin A. An intermediate en route to the total synthesis of shishijimicin A was diverted to the trisaccharide domain of namenamicin by utilizing modern glycosidation methods, which also gained its success in the final coupling with the enediyne warhead and led to, as presented in Chapter 3, the first syntheses of both 7′-epimers of namenamicin. The mysterious stereogenic center at 7′ position of natural namenamicin was unequivocally assigned by 1H NMR analysis on the rigidified polycyclic compounds. Additionally, the implemented semi-pinacol rearrangement within the synthesis of the methylthio sugar fragment has validated the use of 2-deoxy-ribofuranoside as a precursor of 2-deoxy-hexose through a ring expansion strategy, expanding our knowledge and synthetic toolbox in the carbohydrate synthesis.