Sir Robert Robinson's “Anthocyanin Period”: 1922–1934 — A Case Study of an Early Twentieth-Century Natural Products Synthesis

Abstract

Sir Robert Robinson was one of the leading synthetic organic chemists of the twentieth century. His work in both theoretical chemistry and natural product synthesis was pioneering and led to his being awarded the Nobel Prize in chemistry in 1947. His specific accomplishments in terms of chemical structures synthesised and the introduction of new theoretical propositions represented major accomplishments in chemistry in the first half of the twentieth century. As he was one of the leading figures in the emerging field of natural product synthesis, it is a valuable exercise to examine his publication pattern as it pertained to a natural products synthesis project. This pattern manifested itself in the publication of a series of papers over several years, each focused on a specific family of natural products, with the publications first concentrating on simple precursor structures, but quickly moving on to full synthetic procedures for the targeted natural products. This was followed by an exhaustive study of the particular family of compounds. This paper reports one of Robinson's synthetic programmes, namely the synthesis of anthocyanins, which was carried out from 1922 to 1934 and resulted in the publication of forty-seven papers, including one on the first artificial synthesis of a flower pigment. This approach, as outlined in Robinson's publications, to tackling a complex synthetic challenge provides insight into the methodology of one of the leading natural product chemists of the first half of the twentieth century.     

From Decades to Minutes: Steps Toward the Structure of Strychnine 1910–1948 and the Application of Today's Technology

Between 1910 and 1947, Robert Robinson (primarily), among others, published numerous proposed structures for strychnine. Robinson published 17 of his strychnine papers with his doctoral advisor William Henry Perkin, Jr., though all but two appeared after Robinson had taken his first permanent academic position. This Essay analyzes 20 key publications leading up to Robinson's (correct, then incorrect, then correct again though not definitively) proposal and Woodward's assignment of the actual structure of strychnine. We subjected the assignment of the strychnine structure to a modern computational quantum chemistry workflow. By computing, with density functional theory, ¹H and ¹³C NMR chemical shifts for the literature‐proposed strychnine structures, we were able to rule out most incorrect structures. ¹³C NMR predictions were better at this, but ¹H NMR chemical shifts were helpful. A comparison is made between the consequences of publishing erroneous ideas in the first half of the 20th century and doing so in the 21st century.     

From Decades to Minutes: Steps Toward the Structure of Strychnine 1910–1948 and the Application of Today's Technology

Between 1910 and 1947, Robert Robinson (primarily), among others, published numerous proposed structures for strychnine. Robinson published 17 of his strychnine papers with his doctoral advisor William Henry Perkin, Jr., though all but two appeared after Robinson had taken his first permanent academic position. This Essay analyzes 20 key publications leading up to Robinson's (correct, then incorrect, then correct again though not definitively) proposal and Woodward's assignment of the actual structure of strychnine. We subjected the assignment of the strychnine structure to a modern computational quantum chemistry workflow. By computing, with density functional theory, ¹H and ¹³C NMR chemical shifts for the literature-proposed strychnine structures, we were able to rule out most incorrect structures. ¹³C NMR predictions were better at this, but ¹H NMR chemical shifts were helpful. A comparison is made between the consequences of publishing erroneous ideas in the first half of the 20th century and doing so in the 21st century.     

Analytical Applications of Ion-Exchange Materials. V. Chromatographic Separation of Drugs on Ferric Phosphate Papers

Abstract

Chromatography of 14 drugs is performed on papers impregnated with ferric phosphate. Nine solvent systems are used based on aqueous phosphate buffers and mixed organic solvents. The Rf values on plain papers and impregnated are compared. Some important binary separations are practically achieved.     

Research on the change of chemical composition in productive process of Re Du Ning injection by HPLC/Q‐TOF MS

A high‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry (HPLC/Q‐TOF MS) was developed for the analysis of chemical composition change in the production process of Re Du Ning injection, a Chinese medicine preparation with a combination of Lonicera japonica Thunb., Gardenia jasminoides Ellis and Artemisia annua L. A total of 90 compounds from raw materials–intermediates–Re Du Ning injection were detected; among them, 55 compounds were identified or tentatively characterized, and the characteristic ions of different types of compounds were described. Based on these studies, the different types of compounds in the various process routes were analyzed. A total of 28 compounds, including seven iridoid glycosides and six monoterpenes from G. jasminoides Ellis, five iridoid glycosides, nine phenolic acids and one unknown compound from L. japonica Thunb., were transferred to Re Du Ning injection, and two unknown compounds were generated in the production process of Re Du Ning injection. The results indicated that the Chinese Medicine Pharmaceutical process control is very important. This method could provide some reference for other Chinese medicine preparations. Copyright © 2015 John Wiley & Sons, Ltd.     

Polysaccharide Based Vaccines for The Prevention of Pneumococcal Infections

1. INTRODUCTION

Streptococcus pneumoniae remains an important cause of infections in this end of the 20th century and is responsible for invasive diseases - pneumonia, meningitis, bacteremia, septicemia - as well as for noninvasive diseases such as pharyngitis, conjunctivitis, otitis media.^1,2     

Oxazepines and thiazepines. XIX Synthesis of optically active 2,3-dihydro-1,5-benzothiazepin-4(5H)-ones

Optically active 2,3-dihydro-1,5-benzothiazepin-4(5H)-ones (14–17) have been synthesizedvia resolution and chemical transformation of nitrocarboxylic acids6–9. Starting from the latter various optically active substances have been synthesized as well. Optical purity was checked by NMR spectroscopy.Dedicated to Prof. Dr.G. Snatzke on the occasion of his 60th birthday.     

A novel synthesis of N-acetyl-α-d-fucosamine 1-phosphate and uridine 5"-diphospho-N-acetyl-α-d-fucosamine

In connection with studies on the biosynthesis of capsular polysaccharides from Staphylococcus aureus, a new synthesis of uridine 5"-(2-acetamido-2,6-dideoxy--d-galactopyranosyl diphosphate) (uridine 5"-diphospho-N-acetyl--d-fucosamine) using 2-azido-3,4-di-O-acetyl-2,6-dideoxy--d-galactopyranosyl nitrate as the key intermediate was carried out. The reaction of this product with cesium dibenzyl phosphate smoothly affords the corresponding -glycosyl dibenzyl phosphate, which undergoes anomerization on treatment with BF₃·Et₂O and 2-bromopyridine to give -glycosyl dibenzyl phosphate in high yield. This product was then transformed into 2-amino-3,4-di-O-acetyl-2,6-dideoxy--d-galactopyranosyl phosphate, subsequently converted into 2-acetamido-2,6-dideoxy--d-galactopyranosyl phosphate and the target nucleoside diphosphate sugar.     

Ion-Exchange Chromatographic Separation of Anions on Hydrated Bismuth Oxide Impregnated Papers

Abstract

A comparative study of the chromatographic behaviour of anions, iodide, sulphide, phosphate, arsenate, arsenite, vanadate, chroraate, dichromate, thiosulphate, thiocyanate, ferricyanide and ferrocyanide on papers impregnated with hydrated bismuth oxide and untreated Whatman no, 1 papers has been made by employing identical aqueous, non-aqueous and mixed solvent systems. Sharp and compact spots were obtained with impregnated papers whereas the opposite applied to plain papers. Various analytically important binary and ternary separations are reported.     

Mechanical and Chemical Explanations in Du Clos' Chemistry

Abstract

Samuel Cottereau Du Clos (1598–1685) appears as the first French chemist to combine in chemistry (for him, the science of substances, the physics of qualities) demonstrations using the laws of motion with demonstrations using the qualities of chemical principles. In this way, he brought to bear two different and complementary orders of explanation. According to Du Clos, the mechanical considerations represent a first approach, a stage towards the knowledge of “the truth of things” (la vérité des choses) in natural philosophy. He set out his chemistry at the Académie royale des sciences de Paris, especially through his criticism of Boyle's Certain Physiological Essays in 1668–1669.     

pitfalls in Using Filter Paper Disks as Standard Supports In X-Ray Fluorescence Spectrometry

Abstract

Standard solutions of dimethylarsinic acid in water and methanol are deposited on Whatman No. 1 and No. 114 filter papers. The arsenic content is measured by X-ray fluorescence spectrometry. The observed specific count depends on the nature of solvents, the volume of spotting solutions, the method of spotting and the type of filter papers.     

A new dihydrofurocoumarin from the fruits of Pandanus tectorius Parkinson ex Du Roi

From the fruit of Pandanus tectorius Parkinson ex Du Roi, one new dihydrofurocoumarin, named pandanusin A (1) and 15 known compounds, including one furanocoumarin (2), two coumarins (3, 4), four lignans (5–8), one neolignan (9), two flavonoids (10, 11), three phenolics (12–14), one monoglyceride (15) and one monosaccharide (16) were isolated by various chromatography methods. Among them, compounds (3–5) were obtained from the Pandanus genus for the first time and compounds (9–14, 16) were reported from this species for the first time. Their structures were elucidated by HR–ESI–MS, NMR 1D and 2D experiments and comparison with previous reported data. The α-glucosidase inhibitory activity of all compounds was measured. The isolated compounds (1–12, 14) showed better α-glucosidase inhibitory activity (IC₅₀ = 42.2, 36.5, 84.7, 73.2, 40.8, 26.7, 76.5, 33.8, 68.1, 14.4, 22.1, 81.5, 43.8 μM, respectively) than the standard drug acarbose (IC₅₀ = 214.5 μM).