Professor K. C. Nicolaou*Department of Chemistry, The Scripps Research Institute and the University of California, San Diego, 10550 North Torrey Pines Road, La Jolla, California 92037 USA.

Abstract

After numerous near-discoveries of the [42] cycloaddition reaction by several luminaries in the field of organic chemistry during the early part of the 20th century, [1,2] the keen insight of Professor Otto Diels [3] and his student, Kurt Alder, [4] in properly identifying the products (4 and 6, Scheme 1) arising from the reaction of cyclopentadiene (1) with quinone (2) denotes a historic event in the field of chemistry for which these two individuals were rewarded with a reaction that would henceforth bear their names. [5] With prophetic foresight, Diels and Alder clearly anticipated the importance of this discovery in their landmark 1928 paper, particularly as applied to natural product synthesis, through the following remark: ™Thus it appears to us that the possibility of synthesis of complex compounds related to or identical with natural products such as terpenes, sesquiterpenes, perhaps even alkaloids, has been moved to the near prospect.∫ However, in an intriguing moment of scientific territoriality, which might appear slightly off-color or even amusing to a contem-Scheme 1. The discovery of the Diels ± Alder reaction in 1928, a reaction for which the namesakes would receive the Nobel Prize in Chemistry in 1950: Diels the professor, Alder the student.

The Oxetane Ring in Taxol

“…Regrettably, the tubulin assembly assay was not performed for this compound. 38 Consequently, we are obliged to assume that 26 poisons cells by a mechanism analogous to that of Taxol. In an attempt to rationalize the bioresults for the compound, we performed a conformational analysis seeking variation in ring B.…”

Identification of anti-cyanobacterial leads targeting carbonic anhydrase from phytochemical database using in silico approach

“…A phytochemical database of 3K molecules was created, considering the medicinal plants of Odisha via a previously reported literature survey. The toxicity of phytochemicals in the database was investigated, and nontoxic phytochemicals were determined using multi software packages (Molsoft LLC., 2007;Pires et al, 2015). Fifty molecules (Table 1) from 3K molecules followed drug likenesses and ADMET properties (Pires et al, 2015;Tripathi et al, 2019).…”

“…Fifty molecules (Table 1) from 3K molecules followed drug likenesses and ADMET properties (Pires et al, 2015;Tripathi et al, 2019). Among them, the two lead molecules, alpha-tocopherol succinate and mycophenolic acid, showed drug-likeness scores of 0.93 and 0.69, respectively, out of 1 (Molsoft LLC., 2007). The stability and reactivity of the lead molecules were determined by DFT calculations.…”

“…(http://molsoft.com/) to predict the ADMET properties of the molecules present in the prepared database. These search engines predicted the pharmacokinetics of the molecules using the bioavailability radar, which considers six physicochemical properties, including lipophilicity, size, polarity, solubility, flexibility, and saturation, to detect toxicity (Molsoft LLC, 2007;Pires et al, 2015). The Lipinski filter, pioneer rule-of-five, was also used in this tool to predict drug likeness (Tripathi et al, 2019).…”

“…Furthermore, density functional theory (DFT) calculations provide higher occupied molecular orbital (HOMO), lower occupied molecular orbital (LUMO) and frontal orbital (FO), which give a preliminary idea about the reactivity and stability of the molecules (Parr et al, 1922). Additionally, the pk CSM web server was used to calculate the absorption, digestion, metabolism, excretion, and toxicity (ADMET) of the compounds, while SwissADME and Molsoft L.L.C online web servers were used to determine the pharmacokinetic properties of small molecules (Molsoft LLC., 2007;Pires et al, 2015).…”