The Quest for Quinine: Those Who Won the Battles and Those Who Won the War

Abstract

For a long time, the synthesis of quinine constituted an elusive target. In 2004, which marked the 60th anniversary of the publication of the approach used by Woodward and Doering to synthesize quinine, two new stereocontrolled total syntheses of the natural product were accomplished. Together with the well-publicized first stereocontrolled total synthesis of quinine by Stork in 2001, these publications evidence the revival of interest of organic chemists in the synthesis of this compound, once considered a miracle drug. The recently disclosed syntheses of quinine also testify in a remarkable manner the huge progress made by organic synthesis during the last three decades since the first series of partially controlled syntheses of quinine by the group of Uskokovic. Following an account of the historical importance of quinine as an antimalarial drug and a brief description of the experiments which contributed to its isolation and structural elucidation, the first reconstructions of quinine and the total syntheses of the natural product are discussed.

Accurate mass–time tag library for LC/MS-based metabolite profiling of medicinal plants

“…For example, in root extracts of Cinchona pubescens Vahl, in addition to quinine ( 8 ), several other known constituents such as cinchonamine ( 29 ), cinchonine ( 30 ), hydrocinchonine ( 31 ), and hydroquinidine ( 32 ) were tentatively identified (Kaufmann and Rúveda, 2005) (Supplementary Table 3), but other unrelated alkaloids were not found to be present. In Taxus cell cultures, baccatin III ( 33 ), 10-deacetylbaccatin ( 34 ), and cephalomannine ( 35 ) were detected with high confidence, in addition to the anticancer agent taxol ( 1 ) (Ketchum and Croteau, 2006) (Supplementary Table 3).…”

Unexpectedly High Beta-Diversity of Root-Associated Fungal Communities in the Bolivian Andes

“…Whilst it was previously widely distributed, overharvesting for the treatment of fevers has decimated native populations. With the shift in reliance to plantations and the production of synthetic alkaloids, demand for the bark from wild samples has diminished, leaving isolated clusters or individual C. calisaya specimens (Kaufman and Ruveda, 2005). The Yungas mountain forest is today the location of a significant proportion of the remaining endogenous C. calisaya populations.…”

Phylogeny Predicts the Quantity of Antimalarial Alkaloids within the Iconic Yellow Cinchona Bark (Rubiaceae: Cinchona calisaya)

“…Bark from Cinchona trees ( Cinchon a L., Rubiaceae) of the Andean mountain forests produce quinine alkaloids, which were the only effective treatment of malaria for more than four centuries (Honigsbaum, 2001; Kaufman and Ruveda, 2005). The medicinal value of Cinchona bark was first discovered in Loxa (now Loja, Ecuador) in the seventeenth century by Jesuit monks, and soon exports of different varieties of Cinchona pubescens Vahl (red bark) from South America to Europe were reaching half a million kilograms bark per year (Roersch van der Hoogte and Pieters, 2015).…”

“…Cinchona bark and its alkaloids remained the most efficient treatment of malaria until the 1940s when chloroquine and other synthetic antimalarial compounds were developed (Newman et al, 2000; Kaufman and Ruveda, 2005). With the development of resistant malaria strains (Bruce-Chwatt, 1990) the quest for new antimalarial compounds is continuing, and the discovery of artemisinin from a Chinese herbal medicine based on Artemisia annua L. (Tu, 2011), was rewarded with the Nobel prize in medicine in 2015.…”