A Study on Camphor Derivatives and Its Applications: A Mini-Review

: Natural compounds are the prominent sources for the synthesis of abundant biologically active substances in medicinal chemistry. Camphor exists in two enantiomeric forms i.e., R and S, or both, which are readily obtainable. Camphor is a small molecule with chirality property that binds to some active site, together with its low cost and convenience to transform into synthetically useful derivatives and one of the most important monoterpenoids widely spread in plants and has been used as starting material for the various camphor based derivatives which exhibit several biological activities include antimicrobial, antiviral, antioxidant, analgesic and anti-cancer. Many of those simple derivatives are commercially available in the form of camphor sulfonic acid or ketopinic acid that can be easily be produced from camphor. This compound is primarily used as a chiral starting material in the enantiospecific synthesis of natural products is because of its available methods for the direct or indirect introduction of functionality at C-3, C-5, C-8, C-9, and C-10 carbon atoms. In this study, heterocyclic compounds derived from camphor are arranged in different groups as Camphor-Derived Simple Heterocycles, Fused Camphor-Derived Heterocycles, Spiro Camphor-Derived Heterocycles, Ring Expanded Camphor-Derived Heterocycles and Camphor derived metal complexes. This study summarizes the transformations of camphor and its derivatives along with their biological activities.

Practical and Scalable Installation of Neglected S(VI) Functionality with Applications to the Enantiospecific Synthesis of Pharmaceuticals

<p>Sulfoximines and related sulfonimidoyl groups have been largely ignored for decades until their value was demonstrated in biological settings. The realization of their importance has ushered in a new wave of discovery and pharmaceutical applications. In attempts to remove the “neglected” description of the lesser-known S(VI) groups, a practical and modular approach for a-substituted heterocycles bearing sulfonimidoyl functional groups was developed. A variety of sulfoximines containing diverse functionality and complexity were rapidly introduced in an enantiospecific fashion with good to excellent yields. Pharmaceutically important heterocyclic scaffolds were shown to undergo the facile nucleophilic substitution, while sulfoximines, sulfonimidamides and sulfondiimines were all demonstrated to be compatible nucleophiles. The utility and practicality of the method was exhibited in target- and diversity-oriented syntheses of four sulfoximine-containing pharmaceuticals including ceralasertib, an ATR inhibitor currently in clinical trials. The introduction of underexplored sulfur functionality to common heterocyclic pharmacophores provides a practical platform for rapid analog development that is expected to aid future efforts in the discovery sciences.</p>

Practical and Scalable Installation of Neglected S(VI) Functionality with Applications to the Enantiospecific Synthesis of Pharmaceuticals

<p>Sulfoximines and related sulfonimidoyl groups have been largely ignored for decades until their value was demonstrated in biological settings. The realization of their importance has ushered in a new wave of discovery and pharmaceutical applications. In attempts to remove the “neglected” description of the lesser-known S(VI) groups, a practical and modular approach for a-substituted heterocycles bearing sulfonimidoyl functional groups was developed. A variety of sulfoximines containing diverse functionality and complexity were rapidly introduced in an enantiospecific fashion with good to excellent yields. Pharmaceutically important heterocyclic scaffolds were shown to undergo the facile nucleophilic substitution, while sulfoximines, sulfonimidamides and sulfondiimines were all demonstrated to be compatible nucleophiles. The utility and practicality of the method was exhibited in target- and diversity-oriented syntheses of four sulfoximine-containing pharmaceuticals including ceralasertib, an ATR inhibitor currently in clinical trials. The introduction of underexplored sulfur functionality to common heterocyclic pharmacophores provides a practical platform for rapid analog development that is expected to aid future efforts in the discovery sciences.</p>

Practical and Scalable Installation of Neglected S(VI) Functionality with Applications to the Enantiospecific Synthesis of Pharmaceuticals

<p>Sulfoximines and related sulfonimidoyl groups have been largely ignored for decades until their value was demonstrated in biological settings. The realization of their importance has ushered in a new wave of discovery and pharmaceutical applications. In attempts to remove the “neglected” description of the lesser-known S(VI) groups, a practical and modular approach for a-substituted heterocycles bearing sulfonimidoyl functional groups was developed. A variety of sulfoximines containing diverse functionality and complexity were rapidly introduced in an enantiospecific fashion with good to excellent yields. Pharmaceutically important heterocyclic scaffolds were shown to undergo the facile nucleophilic substitution, while sulfoximines, sulfonimidamides and sulfondiimines were all demonstrated to be compatible nucleophiles. The utility and practicality of the method was exhibited in target- and diversity-oriented syntheses of four sulfoximine-containing pharmaceuticals including ceralasertib, an ATR inhibitor currently in clinical trials. The introduction of underexplored sulfur functionality to common heterocyclic pharmacophores provides a practical platform for rapid analog development that is expected to aid future efforts in the discovery sciences.</p>

Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs

Herein, we report the enantiospecific synthesis of two artificial glutamate analogs designed based on IKM-159, an antagonist selective to the AMPA-type ionotropic glutamate receptor. The synthesis features the chiral resolution of the carboxylic acid intermediate by the esterification with ʟ-menthol, followed by a configurational analysis by NMR, conformational calculation, and X-ray crystallography. A mice in vivo assay showed that (2R)-MC-27, with a six-membered oxacycle, is neuroactive, whereas the (2S)-counterpart is inactive. It was also found that TKM-38, with an eight-membered azacycle, is neuronally inactive, showing that the activity is controlled by the ring C.

Isolation, characterization, and docking studies of (Z)-isopropyl 7-((1R, 2R, 3R, 5S)-2-((1E, 3Z)-3-fluoro-4-phenoxybuta-1, 3-dienyl)-3,5- dihydroxycyclopentyl) hept-5-enoate, an Impurity of Tafluprost

Introduction: The origin, isolation, and characterization of (Z)-isopropyl 7-((1R, 2R, 3R, 5S)-2-((1E, 3Z)-3-fluoro4-phenoxybuta-1, 3-dienyl)-3, 5-dihydroxycyclopentyl) hept-5-enoate, an impurity found in the preparation of an antiglaucoma agent-Tafluprost has been described. Materials and Methods: Further, an enantiospecific synthesis of (Z)-isopropyl 7-((1R, 2R, 3R, 5S)-2-((1E, 3Z)-3-fluoro-4- phenoxybuta-1, 3-dienyl)-3, 5-dihydroxycyclopentyl) hept-5-enoate has been revealed using deoxofluorination as a key transformation of the strategy. Results and Discussions: Moreover, the impurity showing anti-glaucoma properties in docking studies with respect to bimatoprost. Conclusion: The extent of our work towards docking studies, the present impurity molecule showing almost the same biological activity with respect to Tafluprost.

Menthyl esterification allows chiral resolution for synthesis of artificial glutamate analogs

Herein we report enantiospecific synthesis of two artificial glutamate analogs designed based on IKM–159, an antagonist selective to AMPA-type ionotropic glutamate receptor. The synthesis features chiral resolution of the carboxylic acid intermediate by esterification with L–menthol, followed by configurational analysis by NMR, conformational calculation, and X–ray crystallography. Mice in vivo assay showed that (2R)–MC–27 with six-membered oxacycle is neuroactive, whereas the (2S)–counterpart is inactive. It was also found that the TKM–38 with eight-membered azacycle is neuronally inactive to suggest the possibility that the analog with a smaller five-membered azacycle may act as a potent agent.