sarabindu roy - Academia.edu (original) (raw)
Papers by sarabindu roy
Molnupiravir (MK-4482, EIDD-2801) is a promising orally bioavailable drug candidate for treatment... more Molnupiravir (MK-4482, EIDD-2801) is a promising orally bioavailable drug candidate for treatment of COVID-19. Herein we describe a supply-centered and chromatography-free synthesis of molnupiravir from cytidine, consisting of two steps: a selective enzymatic acylation followed by transamination to yield the final drug product. Both steps have been successfully performed on decagram scale: the first step at 200 g, and the second step at 80 g. Overall, molnupiravir has been obtained in a 41% overall isolated yield compared to a maximum 17% isolated yield in the patented route. This route provides many advantages to the initial route described in the patent literature and would decrease the cost of this pharmaceutical should it prove safe and efficacious in ongoing clinical trials.
Journal of Medicinal Chemistry, 2011
Highly invasive tumor cells are characterized by a metabolic switch, known as the Warburg effect,... more Highly invasive tumor cells are characterized by a metabolic switch, known as the Warburg effect, from "normal" oxidative phosphorylation to increased glycolysis even under sufficiently oxygenated conditions. This dependence on glycolysis also confers a growth advantage to cells present in hypoxic regions of the tumor. One of the key enzymes involved in glycolysis, the muscle isoform of lactate dehydrogenase (LDH-A), is overexpressed by metastatic cancer cells and is linked to the vitality of tumors in hypoxia. This enzyme may be considered as a potential target for new anticancer agents, since its inhibition cuts cancer energetic and anabolic supply, thus reducing the metastatic and invasive potential of cancer cells. We have discovered new and efficient N-hydroxyindole-based inhibitors of LDH-A, which are isoform-selective (over LDH-B) and competitive with both the substrate (pyruvate) and the cofactor (NADH). The antiproliferative activity of these compounds was confirmed on a series of cancer cell lines, and they proved to be particularly effective under hypoxic conditions. Moreover, NMR experiments showed that these compounds are able to reduce the glucose-tolactate conversion inside the cell.
![Research paper thumbnail of Facile and Scalable Methodology for the Pyrrolo[2,1-f][1,2,4]triazine of Remdesivir](https://attachments.academia-assets.com/90011037/thumbnails/1.jpg)
](Pyrrolo[2,1-f][1,2,4]triazine (1) is an important regulatory starting material in the production ... more Pyrrolo[2,1-f][1,2,4]triazine (1) is an important regulatory starting material in the production of Remdesivir (Veklury®). Compound 1 was produced through a newly developed synthetic methodology utilizing the simple building blocks pyrrole, chloramine and formamidine acetate by examining the mechanistic pathway for the process optimization exercise. Triazine 1 was obtained in 55% overall yield in a two-reactor operated process. This work describes the safety of the process, impurity profiles and control, and efforts towards the scale-up of triazine for the preparation of kilogram quantity.
A scalable four step synthesis of molnupiravir from cytidine is described herein. The attractiven... more A scalable four step synthesis of molnupiravir from cytidine is described herein. The attractiveness of this approach is its fully chemical nature involving inexpensive reagents and more environmentally friendly solvents such as water, isopropanol, acetonitrile and acetone. Isolation and purification procedures are improved in comparison to our earlier report, as all intermediates can be isolated via aqueous acid treatment and recrystallization. The key steps in the synthesis, namely ester formation, hydroxamination and deprotection were done on multigram scale to afford molnupiravir in 36-41% yield with average purity of 98 wt% by q-NMR and 99 area % by HPLC
ACS Omega
Molnupiravir (MK-4482, EIDD-2801) is a promising orally bioavailable drug candidate for the treat... more Molnupiravir (MK-4482, EIDD-2801) is a promising orally bioavailable drug candidate for the treatment of COVID-19. Herein, we describe a supply-centered and chromatographyfree synthesis of molnupiravir from cytidine, consisting of two steps: a selective enzymatic acylation followed by transamination to yield the final drug product. Both steps have been successfully performed on a decagram scale: the first step at 200 g and the second step at 80 g. Overall, molnupiravir has been obtained in a 41% overall isolated yield compared to a maximum 17% isolated yield in the patented route. This route provides many advantages to the initial route described in the patent literature and would decrease the cost of this pharmaceutical should it prove safe and efficacious in ongoing clinical trials.
Helv Chim Acta, 2008
Pd/C is used as an efficient catalyst for the copper-free Sonogashira coupling of acid chlorides ... more Pd/C is used as an efficient catalyst for the copper-free Sonogashira coupling of acid chlorides and terminal alkynes to afford ynones in high yields (Tables 1 and 3). Cyclization of (2-methoxyaryl)substituted ynones induced by I 2 /ammonium cerium(IV) nitrate (CAN) at room temperature gave 3iodochromenones (¼ 3-iodo-4H-1-benzopyran-4-ones) in excellent yield (Table 4).
Catal Commun, 2009
Chloromethylated polystyrene supported ionic liquid is used as catalyst in the aldol-type couplin... more Chloromethylated polystyrene supported ionic liquid is used as catalyst in the aldol-type coupling of a variety of aldehydes with ethyl diazoacetate in water. Moderate to excellent yields of the corresponding a-diazo-b-hydroxy esters were obtained. The catalyst was separated by filtration and reused in five consecutive cycles without any appreciable loss of activity.
Synfacts, 2008
... Contributor(s): Yasuhiro Uozumi, Yutaka Matsuura. PR Likhar*, M. Roy, S. Roy, MS Subhas, ML K... more ... Contributor(s): Yasuhiro Uozumi, Yutaka Matsuura. PR Likhar*, M. Roy, S. Roy, MS Subhas, ML Kantam, B. Sreedhar. Indian Institute of Chemical Technology, Hyderbad, India. ... Georg Thieme Verlag KG Stuttgart - New York. Alle Rechte vorbehalten. Impressum / Disclaimer.
ChemInform, 2009
www.cheminform.wiley-vch.de Carboxylic acid esters Q 0530 Layered-Double-Hydroxide-Supported Rhod... more www.cheminform.wiley-vch.de Carboxylic acid esters Q 0530 Layered-Double-Hydroxide-Supported Rhodium(0): An Efficient and Reusable Catalyst for the Heck-Type Coupling of Alkenes and Arylboronic Acids.-The catalyst can be applied without any external ligand. It is quantitatively recovered by simple filtration and reused for a number of runs with consistent activity.-(ROY, S.;
ChemInform, 2008
Hydroxycarboxylic acids (ether carboxylic acids) and esters Q 0450 Silica-Supported Tetramethylgu... more Hydroxycarboxylic acids (ether carboxylic acids) and esters Q 0450 Silica-Supported Tetramethylguanidine: An Efficient Solid Base for Aldol-Type Coupling of Aldehydes with Ethyl Diazoacetate.-The structure of SSG includes trimethylsilylated surface hydroxyl groups. Various synthetically important α-diazo-−β-hydroxy esters are prepared and the catalyst can be recovered and reused 6 times with almost no loss of activity.-(LIKHAR*,
Advanced Synthesis & Catalysis, 2006
Synfacts, 2008
... Contributor(s): Yasuhiro Uozumi, Yutaka Matsuura. PR Likhar*, M. Roy, S. Roy, MS Subhas, ML K... more ... Contributor(s): Yasuhiro Uozumi, Yutaka Matsuura. PR Likhar*, M. Roy, S. Roy, MS Subhas, ML Kantam, B. Sreedhar. Indian Institute of Chemical Technology, Hyderbad, India. ... Georg Thieme Verlag KG Stuttgart - New York. Alle Rechte vorbehalten. Impressum / Disclaimer.
Molnupiravir (MK-4482, EIDD-2801) is a promising orally bioavailable drug candidate for treatment... more Molnupiravir (MK-4482, EIDD-2801) is a promising orally bioavailable drug candidate for treatment of COVID-19. Herein we describe a supply-centered and chromatography-free synthesis of molnupiravir from cytidine, consisting of two steps: a selective enzymatic acylation followed by transamination to yield the final drug product. Both steps have been successfully performed on decagram scale: the first step at 200 g, and the second step at 80 g. Overall, molnupiravir has been obtained in a 41% overall isolated yield compared to a maximum 17% isolated yield in the patented route. This route provides many advantages to the initial route described in the patent literature and would decrease the cost of this pharmaceutical should it prove safe and efficacious in ongoing clinical trials.
Journal of Medicinal Chemistry, 2011
Highly invasive tumor cells are characterized by a metabolic switch, known as the Warburg effect,... more Highly invasive tumor cells are characterized by a metabolic switch, known as the Warburg effect, from "normal" oxidative phosphorylation to increased glycolysis even under sufficiently oxygenated conditions. This dependence on glycolysis also confers a growth advantage to cells present in hypoxic regions of the tumor. One of the key enzymes involved in glycolysis, the muscle isoform of lactate dehydrogenase (LDH-A), is overexpressed by metastatic cancer cells and is linked to the vitality of tumors in hypoxia. This enzyme may be considered as a potential target for new anticancer agents, since its inhibition cuts cancer energetic and anabolic supply, thus reducing the metastatic and invasive potential of cancer cells. We have discovered new and efficient N-hydroxyindole-based inhibitors of LDH-A, which are isoform-selective (over LDH-B) and competitive with both the substrate (pyruvate) and the cofactor (NADH). The antiproliferative activity of these compounds was confirmed on a series of cancer cell lines, and they proved to be particularly effective under hypoxic conditions. Moreover, NMR experiments showed that these compounds are able to reduce the glucose-tolactate conversion inside the cell.
Pyrrolo[2,1-f][1,2,4]triazine (1) is an important regulatory starting material in the production ... more Pyrrolo[2,1-f][1,2,4]triazine (1) is an important regulatory starting material in the production of Remdesivir (Veklury®). Compound 1 was produced through a newly developed synthetic methodology utilizing the simple building blocks pyrrole, chloramine and formamidine acetate by examining the mechanistic pathway for the process optimization exercise. Triazine 1 was obtained in 55% overall yield in a two-reactor operated process. This work describes the safety of the process, impurity profiles and control, and efforts towards the scale-up of triazine for the preparation of kilogram quantity.
A scalable four step synthesis of molnupiravir from cytidine is described herein. The attractiven... more A scalable four step synthesis of molnupiravir from cytidine is described herein. The attractiveness of this approach is its fully chemical nature involving inexpensive reagents and more environmentally friendly solvents such as water, isopropanol, acetonitrile and acetone. Isolation and purification procedures are improved in comparison to our earlier report, as all intermediates can be isolated via aqueous acid treatment and recrystallization. The key steps in the synthesis, namely ester formation, hydroxamination and deprotection were done on multigram scale to afford molnupiravir in 36-41% yield with average purity of 98 wt% by q-NMR and 99 area % by HPLC
ACS Omega
Molnupiravir (MK-4482, EIDD-2801) is a promising orally bioavailable drug candidate for the treat... more Molnupiravir (MK-4482, EIDD-2801) is a promising orally bioavailable drug candidate for the treatment of COVID-19. Herein, we describe a supply-centered and chromatographyfree synthesis of molnupiravir from cytidine, consisting of two steps: a selective enzymatic acylation followed by transamination to yield the final drug product. Both steps have been successfully performed on a decagram scale: the first step at 200 g and the second step at 80 g. Overall, molnupiravir has been obtained in a 41% overall isolated yield compared to a maximum 17% isolated yield in the patented route. This route provides many advantages to the initial route described in the patent literature and would decrease the cost of this pharmaceutical should it prove safe and efficacious in ongoing clinical trials.
Helv Chim Acta, 2008
Pd/C is used as an efficient catalyst for the copper-free Sonogashira coupling of acid chlorides ... more Pd/C is used as an efficient catalyst for the copper-free Sonogashira coupling of acid chlorides and terminal alkynes to afford ynones in high yields (Tables 1 and 3). Cyclization of (2-methoxyaryl)substituted ynones induced by I 2 /ammonium cerium(IV) nitrate (CAN) at room temperature gave 3iodochromenones (¼ 3-iodo-4H-1-benzopyran-4-ones) in excellent yield (Table 4).
Catal Commun, 2009
Chloromethylated polystyrene supported ionic liquid is used as catalyst in the aldol-type couplin... more Chloromethylated polystyrene supported ionic liquid is used as catalyst in the aldol-type coupling of a variety of aldehydes with ethyl diazoacetate in water. Moderate to excellent yields of the corresponding a-diazo-b-hydroxy esters were obtained. The catalyst was separated by filtration and reused in five consecutive cycles without any appreciable loss of activity.
Synfacts, 2008
... Contributor(s): Yasuhiro Uozumi, Yutaka Matsuura. PR Likhar*, M. Roy, S. Roy, MS Subhas, ML K... more ... Contributor(s): Yasuhiro Uozumi, Yutaka Matsuura. PR Likhar*, M. Roy, S. Roy, MS Subhas, ML Kantam, B. Sreedhar. Indian Institute of Chemical Technology, Hyderbad, India. ... Georg Thieme Verlag KG Stuttgart - New York. Alle Rechte vorbehalten. Impressum / Disclaimer.
ChemInform, 2009
www.cheminform.wiley-vch.de Carboxylic acid esters Q 0530 Layered-Double-Hydroxide-Supported Rhod... more www.cheminform.wiley-vch.de Carboxylic acid esters Q 0530 Layered-Double-Hydroxide-Supported Rhodium(0): An Efficient and Reusable Catalyst for the Heck-Type Coupling of Alkenes and Arylboronic Acids.-The catalyst can be applied without any external ligand. It is quantitatively recovered by simple filtration and reused for a number of runs with consistent activity.-(ROY, S.;
ChemInform, 2008
Hydroxycarboxylic acids (ether carboxylic acids) and esters Q 0450 Silica-Supported Tetramethylgu... more Hydroxycarboxylic acids (ether carboxylic acids) and esters Q 0450 Silica-Supported Tetramethylguanidine: An Efficient Solid Base for Aldol-Type Coupling of Aldehydes with Ethyl Diazoacetate.-The structure of SSG includes trimethylsilylated surface hydroxyl groups. Various synthetically important α-diazo-−β-hydroxy esters are prepared and the catalyst can be recovered and reused 6 times with almost no loss of activity.-(LIKHAR*,
Advanced Synthesis & Catalysis, 2006
Synfacts, 2008
... Contributor(s): Yasuhiro Uozumi, Yutaka Matsuura. PR Likhar*, M. Roy, S. Roy, MS Subhas, ML K... more ... Contributor(s): Yasuhiro Uozumi, Yutaka Matsuura. PR Likhar*, M. Roy, S. Roy, MS Subhas, ML Kantam, B. Sreedhar. Indian Institute of Chemical Technology, Hyderbad, India. ... Georg Thieme Verlag KG Stuttgart - New York. Alle Rechte vorbehalten. Impressum / Disclaimer.