Skip to content
2000
image of An In-depth Analysis of India's API Import Trends in Year 2022-23: Focus on the Top 10 Non-Chinese Sources

Abstract

Background

India and China are pivotal players in the global Active Pharmaceutical Ingredient (API) market, and their interdependence is evident through intricate import-export dynamics within the sector. However, this symbiotic relationship faces stiff competition from counterparts in Europe, the USA, and LATAM. Specific factors drive India's procurement of certain APIs from nations beyond China, significantly impacting the economic landscape of Southern Asia. Interpreting these factors that influence import trends in the API market is necessary to strategize the future API demand-supply.

Objective

This review focuses on the top 10 API imports into India in the year 2022-23 from countries other than China. The aim is to provide a comprehensive understanding of these crucial pharmaceutical components, including their applications, mode of action, and industrial synthesis processes. The review also seeks to illuminate diversification initiatives within India's API sector and unravel the reasons behind substantial import trends for each specific API.

Methods

The process of data collection and its subsequent utilization in analyzing the specific surge in API imports in India during the period of 2020-2022 has been done by five distinct sub-processes: (a) data repossession and preprocessing; (b) development analysis of article publications; (c) distribution analysis of articles by subject, country, application, mode of action and synthesis; (d) scientific teamwork analysis among authors; and (e) development and discovery analysis of research topics. In the review, for each API, a framework has been provided that includes application information, synthesis with reaction scheme, price structure, and the reasons for the high import demand.

Results

The escalation of import volumes of specific Active Pharmaceutical Ingredients (APIs) into India from sources outside of China can be attributed to several key factors. Among these are the implementation of revised Indian internal policies, approval for drug formulation by authorized agencies, a heightened reliance on bio-enzymatic API synthesis processes within Europe in contrast to China, the establishment of new research centers in India, and a notable surge in the incidence of certain diseases within the country. Additionally, India's burgeoning population, coupled with increased consumption of animal-derived food products, has contributed to heightened demand for APIs sourced from alternative markets than the Chinese market. These factors collectively underscore the complexity of the pharmaceutical supply chain and the various influences driving import dynamics within the Indian market.

Conclusion

A thorough examination of API imports into India during the fiscal year 2022-23 has unveiled significant trends, applications, and underlying rationales driving import patterns. The consolidation of manufacturing processes has provided invaluable insights into the synthetic research pathways associated with each API listed. The data serves as a critical resource for stakeholders within the pharmaceutical sector, facilitating informed strategic decision-making and fostering advancements in India's API industry.

Loading

Article metrics loading...

/content/journals/mroc/10.2174/0118756298319158250227113813
2025-04-03
2025-09-15
Loading full text...

Full text loading...

References

  1. S. Strategic Investment Research Unit Harnessing India’s API potential. 2024 Available from: https://www.investindia.gov.in/team-india-blogs/harnessing-indias-api-potential
  2. Confederation of Indian Industry and G. V. Prasad Indian API industry - Reaching the full potential. 2020 Available from: https://agora.mfa.gr/infofiles/%CE%99%CE%9D%CE%94%CE%99%CE%9A%CE%97%20%CE%A6%CE%91%CE%A1%CE%9C%CE%91%CE%9A%CE%95%CE%A5%CE%A4%CE%99%CE%9A%CE%97%20%CE%92%CE%99%CE%9F%CE%9C%CE%97%CE%A7%CE%91%CE%9D%CE%99%CE%91%20in.pdf
  3. Perappadan B.S. India’s import of active pharmaceutical ingredients and key starting material from other countries including China grew: Ministry. 2023 Available from: https://www.thehindu.com/news/national/indias-import-of-active-pharmaceutical-ingredients-and-key-starting-material-from-other-countries-including-china-grew-ministry/article67621117.ece
  4. Gokhale V. Menon S. Madan T. A big-picture look at the India-China relationship. 2024 Available from: https://www.brookings.edu/articles/a-big-picture-look-at-the-india-china-relationship/
  5. Nanda G.B. Survey for novel/ innovative and cost-effective technologies for route of synthesis to decrease the cost of production of apis which are currently being imported to reduce import dependency. 2023 Available from: https://pharmaceuticals.gov.in/sites/default/files/Final%20Report-Survey%20of%20Novel%20Technologies%20for%20Productoion%20of%20APIs.pdf
  6. Sapropterin. 2024 Available from: https://go.drugbank.com/drugs/DB00360
  7. National Library of Medicine Cholic acid - LiverTox: Clinical and research information on drug-induced liver injury. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548276/
  8. Polak Y. Jacobs B.A.W. Bouwhuis N. Hollak C.E.M. Kroon M.A.G.M. Kemper E.M. Product validation and stability testing of pharmacy compounded cholic acid capsules for dutch patients with rare bile acid synthesis defects. Pharmaceutics 2023 15 3 773 10.3390/pharmaceutics15030773 36986634
    [Google Scholar]
  9. Matschiner J.T. The bile acids. The bile acids: Chemistry, physiology, and metabolism in P. Nair P. Kritchevsky D. New York Plenum Press 1971 1 13 14
    [Google Scholar]
  10. Ward A. Brogden R.N. Heel R.C. Speight T.M. Avery G.S. Ursodeoxycholic acid. Drugs 1984 27 2 95 131 10.2165/00003495‑198427020‑00001 6365507
    [Google Scholar]
  11. Leuschner U. Kurtz W. Treatment of primary biliary cirrhosis and cholestatic disorders with ursodeoxycholic acid. Lancet 1987 330 8557 508 10.1016/S0140‑6736(87)91812‑5 2887794
    [Google Scholar]
  12. Mullner S. Hofmann R. Karbe-Thonges B. Saar K. Economic assay for the evaluation of bile acid sequestrants using ox bile and quantitative TLC analysis. J. Planar Chromatogr. Mod. TLC 1992 5 6 408 416
    [Google Scholar]
  13. Roda A. Gatti R. Cavrini V. Cerrè C. Simoni P. HPLC study of the impurities present in different ursodeoxycholic acid preparations: Comparative evaluation of four detectors. J. Pharm. Biomed. Anal. 1993 11 8 751 760 10.1016/0731‑7085(93)80185‑4 8257741
    [Google Scholar]
  14. Scalia S. Cova U. Fogagnolo M. Landi S. Medici A. Determination of free bile acids in raw materials and bulk products by HPLC and GC. Anal. Lett. 1994 27 9 1789 1804 10.1080/00032719408007436
    [Google Scholar]
  15. Lim A.G. Jazrawi R.P. Northfield T.C. The ursodeoxycholic acid story in primary biliary cirrhosis. Gut 1995 37 3 301 304 10.1136/gut.37.3.301 7590420
    [Google Scholar]
  16. Bortolini O. Medici A. Poli S. Biotransformations on steroid nucleus of bile acids. Steroids 1997 62 8-9 564 577 10.1016/S0039‑128X(97)00043‑3 9292932
    [Google Scholar]
  17. Bodge M. Cumpston A. Pharmacology of drugs used in hematopoietic cell transplantation. Hematopoietic Cell Transplantation for Malignant Conditions. Elsevier 2019 19 35 10.1016/B978‑0‑323‑56802‑9.00002‑X
    [Google Scholar]
  18. Achufusi T.G.O. Safadi A.O. Mahabadi N. Ursodeoxycholic acid. StatPearls StatPearls Publishing Treasure Island (FL) 2024
    [Google Scholar]
  19. Roda E. Bazzoli F. Morselli Labate A.M. Mazzella G. Roda A. Sama C. Festi D. Aldini R. Taroni F. Barbara L. Ursodeoxycholic acid vs. chenodeoxycholic acid as cholesterol gallstone-dissolving agents: A comparative randomized study. Hepatology 1982 2 6 804 810 10.1002/hep.1840020611 7141392
    [Google Scholar]
  20. Kanazawa T. Shimazaki A. Sato T. Hoshino T. Syntheses of Ursodesoxycholic acid and its conjugated bile acid. Proc. Jpn. Acad. 1954 30 5 391 392 10.2183/pjab1945.30.391
    [Google Scholar]
  21. Hofmann A.F. Lundgren G. Theander O. Brimacombe J.S. Cook M.C. The preparation of chenodeoxycholic acid and its glycine and taurine conjugates. Acta Chem. Scand. 1963 17 173 186 10.3891/acta.chem.scand.17‑0173
    [Google Scholar]
  22. Dangate P.S. Salunke C.L. Akamanchi K.G. Regioselective oxidation of cholic acid and its 7β epimer by using o-iodoxybenzoic acid. Steroids 2011 76 12 1397 1399 10.1016/j.steroids.2011.07.009 21820458
    [Google Scholar]
  23. Eggert T. Bakonyi D. Hummel W. Enzymatic routes for the synthesis of ursodeoxycholic acid. J. Biotechnol. 2014 191 11 21 10.1016/j.jbiotec.2014.08.006 25131646
    [Google Scholar]
  24. Carrea G. Pilotti A. Riva S. Canzi E. Ferrari A. Enzymatic synthesis of 12-ketoursodeoxycholic acid from dehydrocholic acid in a membrane reactor. Biotechnol. Lett. 1992 14 12 1131 1134 10.1007/BF01027015
    [Google Scholar]
  25. Bovara R. Carrea G. Riva S. Secundo F. A new enzymatic route to the synthesis of 12-ketoursodeoxycholic acid. Biotechnol. Lett. 1996 18 3 10.1007/BF00142949
    [Google Scholar]
  26. Bakonyi D. Wirtz A. Hummel W. Large-scale enzymatic synthesis of 12-ketoursodeoxycholic acid from dehydrocholic acid by simultaneous combination of 3α-hydroxysteroid dehydrogenase from pseudomonas testosteroni and 7β-hydroxysteroid dehydrogenase from collinsella aerofaciens. Z. Naturforsch. B. J. Chem. Sci. 2012 67 10 1037 1044 10.5560/znb.2012‑0165
    [Google Scholar]
  27. Braun M. Sun B. Anselment B. Weuster-Botz D. Novel whole-cell biocatalysts with recombinant hydroxysteroid dehydrogenases for the asymmetric reduction of dehydrocholic acid. Appl. Microbiol. Biotechnol. 2012 95 6 1457 1468 10.1007/s00253‑012‑4072‑6 22581067
    [Google Scholar]
  28. Liu L. Braun M. Gebhardt G. Weuster-Botz D. Gross R. Schmid R.D. One-step synthesis of 12-ketoursodeoxycholic acid from dehydrocholic acid using a multienzymatic system. Appl. Microbiol. Biotechnol. 2013 97 2 633 639 10.1007/s00253‑012‑4340‑5 22899496
    [Google Scholar]
  29. Sun B. Kantzow C. Bresch S. Castiglione K. Weuster-Botz D. Multi‐enzymatic one‐pot reduction of dehydrocholic acid to 12‐keto‐ursodeoxycholic acid with whole‐cell biocatalysts. Biotechnol. Bioeng. 2013 110 1 68 77 10.1002/bit.24606 22806613
    [Google Scholar]
  30. Monti D. Ferrandi E.E. Zanellato I. Hua L. Polentini F. Carrea G. Riva S. One‐pot multienzymatic synthesis of 12‐ketoursodeoxycholic acid: subtle cofactor specificities rule the reaction equilibria of five biocatalysts working in a row. Adv. Synth. Catal. 2009 351 9 1303 1311 10.1002/adsc.200800727
    [Google Scholar]
  31. Giovannini P.P. Grandini A. Perrone D. Pedrini P. Fantin G. Fogagnolo M. 7α- and 12α-Hydroxysteroid dehydrogenases from Acinetobacter calcoaceticus lwoffii: A new integrated chemo-enzymatic route to ursodeoxycholic acid. Steroids 2008 73 14 1385 1390 10.1016/j.steroids.2008.06.013 18674553
    [Google Scholar]
  32. Rukmini S. Cattle slaughter, in varying degrees. 2021 Available from: https://www.thehindu.com/news/national/cattle-slaughter-in-varying-degrees/article62070533.ece
  33. Leading to make a difference. 2023 Available from: https://www.abbott.co.in/content/dam/corp/abbott/en-ind/pdf/agm/Annual-Report-2022-23.pdf
  34. Fanet H. Capuron L. Castanon N. Calon F. Vancassel S. Tetrahydrobiopterin (BH4) pathway: From metabolism to neuropsychiatry. Curr Neuropharmacol. 2021 19 5 591 609 10.2174/1570159X18666200729103529
    [Google Scholar]
  35. Chalupsky K. Kračun D. Kanchev I. Bertram K. Görlach A. Folic acid promotes recycling of tetrahydrobiopterin and protects against hypoxia-induced pulmonary hypertension by recoupling endothelial nitric oxide synthase. Antioxid. Redox Signal. 2015 23 14 1076 1091 10.1089/ars.2015.6329 26414244
    [Google Scholar]
  36. Volza Grow Global World Sapropterin Imports: Overview. Available from: https://www.volza.com/p/sapropterin/import/
  37. Perappadan B.S. Generic drugs to treat four rare diseases launched. 2023 Available from: https://www.thehindu.com/sci-tech/health/four-generic-made-in-india-drugs-to-treat-rare-diseases-offer-relief-for-patients-more-in-pipeline/article67570839.ece
  38. Eichwald T. da Silva L.B. Staats Pires A.C.S. Niero L. Schnorrenberger E. Filho C.C. Espíndola G. Huang W.L. Guillemin G.J. Abdenur J.E. Latini A. Tetrahydrobiopterin: Beyond its traditional role as a cofactor. Antioxidants 2023 12 5 1037 10.3390/antiox12051037 37237903
    [Google Scholar]
  39. Konakanchi D.P. Novel process for the preparation of sapropterin dihydrochloride and its key intermediate, l-biopterin. Patent WO2016189542A1, 2015
  40. Schircks B. Bieri J.H. Viscontini M. Uber Pterinchemie. 60. Read more [1]. Eine neue, regiospezifische synthese von L-Biopterin. Helv. Chim. Acta 1977 60 1 211 214 10.1002/hlca.19770600125
    [Google Scholar]
  41. Schircks B. Bieri J.H. Viscontini M. Über Pterinchemie. 65 Mitteilung [1]. Herstellung von (6 R, S )‐5,6,7,8‐Tetrahydro‐ L ‐biopterin, 7,8‐Dihydro‐ L ‐biopterin, L ‐Sepiapterin, Deoxysepiapterin, (6 R, S )‐5,6‐Dihydrodeoxysepiapterin und 2′‐Deoxybiopterin. Helv. Chim. Acta 1978 61 7 2731 2738 10.1002/hlca.19780610741
    [Google Scholar]
  42. Furrer H.J. Bieri J.H. Viscontini M. Über Pterinchemie. 72. Mitteilung. Trennung der Diastereomeren (6 R )‐ und (6 S )‐5,6,7,8‐Tetrahydro‐ L ‐biopterin. Helv. Chim. Acta 1979 62 8 2577 2580 10.1002/hlca.19790620811
    [Google Scholar]
  43. Rudolf M. Viola G. Andreas S. Martin P. Dirk S. Processes for preparing tetrahydrobiopterin, and analogs of tetrahydrobiopterin. Patent WO2005049614, 2005
  44. Henderson M. Method of synthesizing tetrahydrobiopterin. 2010 Available from: https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2009088979
  45. Wang Z. Zhao D. Wang W. Lan J. You J. Preparation process of (6r)-tetrahydrobiopterin hydrochloride, 2011 Available from: https://patents.google.com/patent/US20130197222A1/en?oq=US20130197222
  46. Patterson E.L. Broquist H.P. Albrecht A.M. von Saltza M.H. Stokstad E.L.R. A new pteridine in urine required for the growth of the protozoon Crithidia fasciculata. J. Am. Chem. Soc. 1955 77 11 3167 3168 10.1021/ja01616a096
    [Google Scholar]
  47. Patterson E.L. Milstrey R. Stokstad E.L.R. The synthesis of a pteridine required for the growth of Crithidia fasciculata. J. Am. Chem. Soc. 1956 78 22 5868 5871 10.1021/ja01603a043
    [Google Scholar]
  48. Joseph W. Process for the synthesis of biopterin. 1974 Available from: https://patents.google.com/patent/US3505329A/en
  49. Tazawa S. Method for producing L-biopterin. 2005 Available from: https://patents.google.com/patent/US7361759B2/en?oq=US7361759
  50. Haruhiko K. Kenji M. Process for the preparation of pterin derivatives. 1989 Available from: https://patents.google.com/patent/US5043446A/en?oq=US5043446+
  51. Mori K. Kikuchi H. A new synthesis of (‐)‐Biopterin employing 5‐Deoxy‐ L ‐ribose as a key intermediate. Liebigs Ann. Chem. 1989 1989 12 1267 1269 10.1002/jlac.1989198902102
    [Google Scholar]
  52. Manuela C. Franzen N. Process for the preparation of (1s,4r)-2-oxa-3-azabicyclo[2,2.1]hept-5-enes. 2010 Available from: https://patents.google.com/patent/US20120157671A1/en?oq=US20120157671
  53. Viscontini M. Provenzale R. Fluoreszierende stoffe aus Drosophila melanogaster. 14. Mitteilung [1]. Eine Synthese des Biopterins. Helv. Chim. Acta 1969 52 5 1225 1228 10.1002/hlca.19690520507
    [Google Scholar]
  54. Sugimoto T. Matsuura S. The convenient syntheses of biopterin and its three opitical isomers. Bull. Chem. Soc. Jpn. 1975 48 12 3767 3768 10.1246/bcsj.48.3767
    [Google Scholar]
  55. Kikuchi H. Mori K. Synthesis of ( – )-biopterin using ( S )-ethyl lactate as a starting material. Agric. Biol. Chem. 1989 53 8 2095 2100 10.1080/00021369.1989.10869605
    [Google Scholar]
  56. Haruhiko K. Mori K. Production of l-biopterin. Patent JP01-221380 1989
  57. Kurono M. Suzuki T. Ogasawara T. Ohishi N. Yagi K. Intermediates for synthesizing BH4 and its derivatives. Patent US5037981, 1990
  58. Murata S. Sugimoto T. Ogiwara S. Mogi K. Wasada H. Novel regio- and stereoselective synthesis of 6-substituted pteridines and naturally occurring L- erythro -biopterin. Synthesis 1992 1992 3 303 308 10.1055/s‑1992‑26097
    [Google Scholar]
  59. Fernandez A.M. Duhamel L. Total synthesis of l-biopterin from l-tartaric acid via 5-deoxy-l-arabinose. J. Org. Chem. 1996 61 24 8698 8700 10.1021/jo961426s
    [Google Scholar]
  60. Thöny B. Auerbach G. Blau N. Tetrahydrobiopterin biosynthesis, regeneration and functions. Biochem. J. 2000 347 1 1 16 10.1042/bj3470001 10727395
    [Google Scholar]
  61. Nazarian S. Akhondi H. Minocycline. StatPearls. [Internet]. StatPearls Publishing 2023
    [Google Scholar]
  62. American Society of Health-System Pharmacists Comparison of doxycycline and minocycline. Available from: https://www.ashp.org/-/media/assets/drug-shortages/docs/drug-shortages-comparison-of-doxycycline-and-minocycline.pdf
  63. Invest India Industry Scenario: The pharmaceutical industry in India is expected to reach $65 Bn by 2024 and to $130 Bn by 2030. Available from: https://www.investindia.gov.in/sector/pharmaceuticals
  64. Minocycline hydrochloride import data under hs code 29419090 with price. Available from: https://www.seair.co.in/minocycline-hydrochloride-import-data/hs-code-29419090.aspx
  65. Koza D.J. Nsiah Y.A. Palladium catalyzed C-N bond formation in the synthesis of 7-amino-substituted tetracyclines. J. Org. Chem. 2002 67 14 5025 5027 10.1021/jo0256585 12098331
    [Google Scholar]
  66. Joseph P. Howard B.J. 7-and 9-alkylamino-6-deoxytetracycline. Patent US3226436A, 1965
  67. Robert W. Henry Marcel K. Substituted 7- and/or 9-amino tetracyclines. Patent US3345410A, 1967
  68. Martell M.J. Jr Boothe J.H. Alkylated Aminotetracyclines Possessing Unique Antibacterial Activity The 6-Deoxytetracyclines. VII. J. Med. Chem. 1967 10 1 44 46 10.1021/jm00313a009 6031702
    [Google Scholar]
  69. Church R.F.R. Schaub R.E. Weiss M.J. Synthesis of 7-dimethylamino-6-demethyl-6-deoxytetracycline (minocycline) via 9-nitro-6-demethyl-6-deoxytetracycline. J. Org. Chem. 1971 36 5 723 725 10.1021/jo00804a025 5545572
    [Google Scholar]
  70. Devadiga S.J. Bharate S.S. Recent developments in the management of Huntington’s disease. Bioorg. Chem. 2022 120 105642 10.1016/j.bioorg.2022.105642 35121553
    [Google Scholar]
  71. Charest M.G. Lerner C.D. Brubaker J.D. Siegel D.R. Myers A.G. A convergent enantioselective route to structurally diverse 6-deoxytetracycline antibiotics. Science 2005 308 5720 395 398 10.1126/science.1109755 15831754
    [Google Scholar]
  72. Sun C. Wang Q. Brubaker J.D. Wright P.M. Lerner C.D. Noson K. Charest M. Siegel D.R. Wang Y.M. Myers A.G. A robust platform for the synthesis of new tetracycline antibiotics. J. Am. Chem. Soc. 2008 130 52 17913 17927 10.1021/ja806629e 19053822
    [Google Scholar]
  73. Codeine. Available from: https://go.drugbank.com/drugs/DB00318
  74. U.S. Food & Drug Administration Codeine information. Available from: https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/codeine-information#:~:text=Codeine%20is%20an%20opioid%20pain,some%20cough%20and%20cold%20medications
  75. Asthana S.N. The cultivation of the opium poppy in India: United Nations office on drugs and crime. Available from: https://www.unodc.org/unodc/en/data-and-analysis/bulletin/bulletin_1954-01-01_3_page002.html
  76. Malm H. Borisch C. Analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, and antigout medications. Drugs During Pregnancy and Lactation. Elsevier 2015 27 58 10.1016/B978‑0‑12‑408078‑2.00002‑0
    [Google Scholar]
  77. Henry N. Cough syrup deaths: India bans anti-cold drug combination for children below four 2023 Available from: https://www.bbc.com/news/world-asia-india-67783377
    [Google Scholar]
  78. Nagase H. Fujii H. Opioids in preclinical and clinical trials. 2010 10.1007/128_2010_74
    [Google Scholar]
  79. Brossi A. The chemistry and pharmacology of morphinan alkaloids. In: The Chemistry and Biology of Isoquinoline Alkaloids Springer Berlin Heidelberg Berlin, Heidelberg 1985 171 190 10.1007/978‑3‑642‑70128‑3_11
    [Google Scholar]
  80. Li Q. Zhang H. Total synthesis of codeine. Chemistry 2015 21 46 16379 16382 10.1002/chem.201503594 26428413
    [Google Scholar]
  81. Nakashima J. Preuss C.V. Mesalamine (USAN). StatPearls. Treasure Island, FL StatPearls Publishing
    [Google Scholar]
  82. Karagozian R. Burakoff R. The role of mesalamine in the treatment of ulcerative colitis. Ther. Clin. Risk Manag. 2007 3 5 893 903 18473013
    [Google Scholar]
  83. Vanzo T. 25 most polluted cities in the world (2023 Rankings). Available from: https://smartairfilters.com/en/blog/25-most-polluted-cities-world-2023-rankings/
  84. Gulveen A. India extends anti-dumping duty on melamine, vitrified tile imports from China. 2021 Available from: https://economictimes.indiatimes.com/news/economy/foreign-trade/india-extends-anti-dumping-duty-on-melamine-vitrified-tile-imports-from-china/articleshow/81213433.cms?from=mdr
  85. World O.E.C. Melamine in India. Available from: https://oec.world/en/profile/bilateral-product/melamine/reporter/ind
  86. Zeng P. Xiong H. Jianmin W. Da L. A kind of mesalazine industrialized process for preparing. Patent CN107778189A, 2016
  87. Healthdirect Australia Limited Cefalexin (Cephalexin). Available from: https://www.healthdirect.gov.au/cephalexin#:~:text=Cefalexin%20(cephalexin)%20is%20an%20antibiotic,soft%20tissue%2C%20kidneys%20and%20bladder
  88. Durbin K. Cephalexin. Available from: https://www.drugs.com/cephalexin.html
  89. Fan Y. Li Y. Liu Q. Efficient enzymatic synthesis of cephalexin in suspension aqueous solution system. Biotechnol. Appl. Biochem. 2021 68 1 136 147 10.1002/bab.1903 32100895
    [Google Scholar]
  90. Mateo C. Recent advances in the industrial enzymatic synthesis of semi-synthetic β-lactam antibiotics. MCRO 2005 2 3 207 218 10.2174/1567203054065691
    [Google Scholar]
  91. Bruggink A. Roos E.C. de Vroom E. Penicillin acylase in the industrial production of β-lactam antibiotics. Org. Process Res. Dev. 1998 2 2 128 133 10.1021/op9700643
    [Google Scholar]
  92. Hyun C.K. Choi J.H. Kim J.H. Ryu D.D.Y. Enhancement effect of polyethylene glycol on enzymatic synthesis of cephalexin. Biotechnol. Bioeng. 1993 41 6 654 658 10.1002/bit.260410608 18609601
    [Google Scholar]
  93. Hyun C.K. Kim J.H. Ryu D.D.Y. Enhancement effect of water activity on enzymatic synthesis of cephalexin. Biotechnol. Bioeng. 1993 42 7 800 806 10.1002/bit.260420703 18613126
    [Google Scholar]
  94. van Langen L.M. de Vroom E. van Rantwijk F. Sheldon R. Enzymatic synthesis of β‐lactam antibiotics using penicillin‐G acylase in frozen media. FEBS Lett. 1999 456 1 89 92 10.1016/S0014‑5793(99)00939‑4 10452536
    [Google Scholar]
  95. Aguirre C. Toledo M. Medina V. Illanes A. Effect of cosolvent and pH on the kinetically controlled synthesis of cephalexin with immobilised penicillin acylase. Process Biochem. 2002 38 3 351 360 10.1016/S0032‑9592(02)00092‑4
    [Google Scholar]
  96. Illanes A. Anjarí S. Arrieta R. Aguirre C. Optimization of yield in kinetically controlled synthesis of ampicillin with immobilized penicillin acylase in organic media. Appl. Biochem. Biotechnol. 2002 97 3 165 180 10.1385/ABAB:97:3:165 11998841
    [Google Scholar]
  97. Schroën C.G.P.H. Nierstrasz V.A. Bosma R. Kemperman G.J. Strubel M. Ooijkaas L.P. Beeftink H.H. Tramper J. In situ product removal during enzymatic cephalexin synthesis by complexation. Enzyme Microb. Technol. 2002 31 3 264 273 10.1016/S0141‑0229(02)00113‑8
    [Google Scholar]
  98. Wei D.Z. Zhu J.H. Cao X.J. Enzymatic synthesis of cephalexin in aqueous two-phase systems. Biochem. Eng. J. 2002 11 2-3 95 99 10.1016/S1369‑703X(02)00032‑3
    [Google Scholar]
  99. Illanes A. Cabrera Z. Wilson L. Aguirre C. Synthesis of cephalexin in ethylene glycol with glyoxyl-agarose immobilised penicillin acylase: Temperature and pH optimisation. Process Biochem. 2003 39 1 111 117 10.1016/S0032‑9592(03)00031‑1
    [Google Scholar]
  100. Illanes A. Anjarí M.S. Altamirano C. Aguirre C. Optimization of cephalexin synthesis with immobilized penicillin acylase in ethylene glycol medium at low temperatures. J. Mol. Catal., B Enzym. 2004 30 2 95 103 10.1016/j.molcatb.2004.01.020
    [Google Scholar]
  101. Xuejun C. Jianhang Z. Dongzhi W. Byung-Ki H. Biosynthesis of Cephalexin in PEG400-Ammonium Sulfate and PEG400-Magnesium Sulfate aqueous two-phase systems. Korean Society for Microbiology and Biotechnology 2004 14 1 62 67
    [Google Scholar]
  102. Aguirre C. Opazo P. Venegas M. Riveros R. Illanes A. Low temperature effect on production of ampicillin and cephalexin in ethylene glycol medium with immobilized penicillin acylase. Process Biochem. 2006 41 9 1924 1931 10.1016/j.procbio.2006.03.045
    [Google Scholar]
  103. Basso A. Spizzo P. Toniutti M. Ebert C. Linda P. Gardossi L. Kinetically controlled synthesis of ampicillin and cephalexin in highly condensed systems in the absence of a liquid aqueous phase. J. Mol. Catal., B Enzym. 2006 39 1-4 105 111 10.1016/j.molcatb.2006.01.029
    [Google Scholar]
  104. Dengchao L. Yewang Z. Shiwei C. Qiong G. Wei D. Enhanced enzymatic production of cephalexin at high substrate concentration with in situ product removal by complexation. Food Technol. Biotechnol. 2008 46 4 461 466
    [Google Scholar]
  105. Aguirre C. Concha I. Vergara J. Riveros R. Illanes A. Partition and substrate concentration effect in the enzymatic synthesis of cephalexin in aqueous two-phase systems. Process Biochem. 2010 45 7 1163 1167 10.1016/j.procbio.2010.03.002
    [Google Scholar]
  106. Bernardino S.M.S.A. Fernandes P. Fonseca L.P. Improved specific productivity in cephalexin synthesis by immobilized PGA in silica magnetic micro‐particles. Biotechnol. Bioeng. 2010 107 5 753 762 10.1002/bit.22867 20632377
    [Google Scholar]
  107. Bahamondes C. Wilson L. Aguirre C. Illanes A. Comparative study of the enzymatic synthesis of cephalexin at high substrate concentration in aqueous and organic media using statistical model. Biotechnol. Bioprocess Eng.; BBE 2012 17 4 711 721 10.1007/s12257‑011‑0674‑6
    [Google Scholar]
  108. Zhou H. Li W. Shou Q. Gao H. Xu P. Deng F. Liu H. Immobilization of penicillin G acylase on magnetic nanoparticles modified by ionic liquids. Chin. J. Chem. Eng. 2012 20 1 146 151 10.1016/S1004‑9541(12)60374‑7
    [Google Scholar]
  109. Li S. Cao X. Enzymatic synthesis of Cephalexin in recyclable aqueous two-phase systems composed by two pH responsive polymers. Biochem. Eng. J. 2014 90 301 306 10.1016/j.bej.2014.06.002
    [Google Scholar]
  110. Pan X. Wang L. Ye J. Qin S. He B. Efficient synthesis of β-lactam antibiotics with very low product hydrolysis by a mutant Providencia rettgeri penicillin G acylase. Appl. Microbiol. Biotechnol. 2018 102 4 1749 1758 10.1007/s00253‑017‑8692‑8 29306966
    [Google Scholar]
  111. Lee D.C. Kim H.S. Optimization of a heterogeneous reaction system for the production of optically activeD-amino acids using thermostableD-hydantoinase. Biotechnol. Bioeng. 1998 60 6 729 738 10.1002/(SICI)1097‑0290(19981220)60:6<729::AID‑BIT9>3.0.CO;2‑G 10099482
    [Google Scholar]
  112. Erbeldinger M. Ni X. Halling P.J. Kinetics of enzymatic solid-to-solid peptide synthesis: Synthesis ofZ-aspartame and control of acid-base conditions by using inorganic salts. Biotechnol. Bioeng. 2001 72 1 69 76 10.1002/1097‑0290(20010105)72:1<69::AID‑BIT10>3.0.CO;2‑P 11084596
    [Google Scholar]
  113. Ulijn R.V. Janssen A.E.M. Moore B.D. Halling P.J. Predicting when precipitation-driven synthesis is feasible: Application to biocatalysis. Chemistry 2001 7 10 2089 2098 10.1002/1521‑3765(20010518)7:10<2089::AID‑CHEM2089>3.0.CO;2‑C 11411981
    [Google Scholar]
  114. Chaiwut P. Kanasawud P. Halling P.J. Solid-to-solid peptide synthesis by glycyl endopeptidase. Enzyme Microb. Technol. 2007 40 4 954 960 10.1016/j.enzmictec.2006.07.042
    [Google Scholar]
  115. Youshko M.I. van Langen L.M. de Vroom E. Moody H.M. van Rantwijk F. Sheldon R.A. Švedas V.K. Penicillin acylase-catalyzed synthesis of ampicillin in “aqueous solution–precipitate” systems. High substrate concentration and supersaturation effect. J. Mol. Catal., B Enzym. 2000 10 5 509 515 10.1016/S1381‑1177(00)00091‑6
    [Google Scholar]
  116. WHO Country Office Antimicrobial resistance and its containment in India. 2016 Available from: https://www.who.int/docs/default-source/searo/india/antimicrobial-resistance/amr-containment.pdf?sfvrsn=2d7c49a2_2
  117. Koovapra S. Bandyopadhyay S. Das G. Bhattacharyya D. Banerjee J. Mahanti A. Samanta I. Nanda P.K. Kumar A. Mukherjee R. Dimri U. Singh R.K. Molecular signature of extended spectrum β-lactamase producing Klebsiella pneumoniae isolated from bovine milk in eastern and north-eastern India. Infect. Genet. Evol. 2016 44 395 402 10.1016/j.meegid.2016.07.032 27473782
    [Google Scholar]
  118. Kar D. Bandyopadhyay S. Bhattacharyya D. Samanta I. Mahanti A. Nanda P.K. Mondal B. Dandapat P. Das A.K. Dutta T.K. Bandyopadhyay S. Singh R.K. Molecular and phylogenetic characterization of multidrug resistant extended spectrum beta-lactamase producing Escherichia coli isolated from poultry and cattle in Odisha, India. Infect. Genet. Evol. 2015 29 82 90 10.1016/j.meegid.2014.11.003 25445661
    [Google Scholar]
  119. Samanta I. Joardar S.N. Das P.K. Sar T.K. Bandyopadhyay S. Dutta T.K. Sarkar U. Prevalence and antibiotic resistance profiles ofSalmonella serotypes isolated from backyard poultry flocks in West Bengal, India. J. Appl. Poult. Res. 2014 23 3 536 545 10.3382/japr.2013‑00929
    [Google Scholar]
  120. Deekshit V.K. Kumar B.K. Rai P. Srikumar S. Karunasagar I. Karunasagar I. Detection of class 1 integrons in Salmonella Weltevreden and silent antibiotic resistance genes in some seafood-associated nontyphoidal isolates of Salmonella in south-west coast of India. J. Appl. Microbiol. 2012 112 6 1113 1122 10.1111/j.1365‑2672.2012.05290.x 22443444
    [Google Scholar]
  121. Kumar P.A. Patterson J. Karpagam P. Multiple Antibiotic Resistance Profiles of Vibrio cholerae non-O1 and non-O139. Jpn. J. Infect. Dis. 2009 62 3 230 232 10.7883/yoken.JJID.2009.230 19468189
    [Google Scholar]
  122. Patel S. Saw S. Daptomycin StatPearls StatPearls Publishing Treasure Island (FL) 2024
    [Google Scholar]
  123. Lam H.Y. Zhang Y. Liu H. Xu J. Wong C.T.T. Xu C. Li X. Total synthesis of daptomycin by cyclization via a chemoselective serine ligation. J. Am. Chem. Soc. 2013 135 16 6272 6279 10.1021/ja4012468 23560543
    [Google Scholar]
  124. Nguyen K.T. Ritz D. Gu J.Q. Alexander D. Chu M. Miao V. Brian P. Baltz R.H. Combinatorial biosynthesis of novel antibiotics related to daptomycin. Proc. Natl. Acad. Sci. USA 2006 103 46 17462 17467 10.1073/pnas.0608589103 17090667
    [Google Scholar]
  125. Grünewald J. Sieber S.A. Mahlert C. Linne U. Marahiel M.A. Synthesis and derivatization of daptomycin: A chemoenzymatic route to acidic lipopeptide antibiotics. J. Am. Chem. Soc. 2004 126 51 17025 17031 10.1021/ja045455t 15612741
    [Google Scholar]
  126. Hill J. Siedlecki J. Parr I. Morytko M. Yu X. Zhang Y. Silverman J. Controneo N. Laganas V. Li T. Lai J.J. Keith D. Shimer G. Finn J. Synthesis and biological activity of N-Acylated ornithine analogues of daptomycin. Bioorg. Med. Chem. Lett. 2003 13 23 4187 4191 10.1016/j.bmcl.2003.07.019 14622998
    [Google Scholar]
  127. Zhang Y. Xu C. Lam H.Y. Lee C.L. Li X. Protein chemical synthesis by serine and threonine ligation. Proc. Natl. Acad. Sci. USA 2013 110 17 6657 6662 10.1073/pnas.1221012110 23569249
    [Google Scholar]
  128. Xu B. Hermant Y. Yang S.H. Harris P.W.R. Brimble M.A. A versatile boc solid phase synthesis of daptomycin and analogues using site specific, on‐resin ozonolysis to install the kynurenine residue. Chemistry 2019 25 62 14101 14107 10.1002/chem.201903725 31429133
    [Google Scholar]
  129. Lam H.Y. Gaarden R.I. Li X. A journey to the total synthesis of daptomycin. Chem. Rec. 2014 14 6 1086 1099 10.1002/tcr.201402049 25205345
    [Google Scholar]
  130. Wong C.T.T. Lam H.Y. Li X. Effective synthesis of kynurenine-containing peptides via on-resin ozonolysis of tryptophan residues: Synthesis of cyclomontanin B. Org. Biomol. Chem. 2013 11 43 7616 7620 10.1039/c3ob41631c 24104948
    [Google Scholar]
  131. Hamada Y. Shioiri T. Recent progress of the synthetic studies of biologically active marine cyclic peptides and depsipeptides. Chem. Rev. 2005 105 12 4441 4482 10.1021/cr0406312 16351050
    [Google Scholar]
  132. von Nussbaum F. Anlauf S. Benet-Buchholz J. Häbich D. Köbberling J. Musza L. Telser J. Rübsamen-Waigmann H. Brunner N.A. Structure and total synthesis of lysobactin (katanosin B). Angew. Chem. Int. Ed. 2007 46 12 2039 2042 10.1002/anie.200604232 17211904
    [Google Scholar]
  133. Guzman-Martinez A. Lamer R. VanNieuwenhze M.S. Total synthesis of lysobactin. J. Am. Chem. Soc. 2007 129 18 6017 6021 10.1021/ja067648h 17432854
    [Google Scholar]
  134. Wohlrab A. Lamer R. VanNieuwenhze M.S. Total synthesis of plusbacin A3: A depsipeptide antibiotic active against vancomycin-resistant bacteria. J. Am. Chem. Soc. 2007 129 14 4175 4177 10.1021/ja068455x 17371023
    [Google Scholar]
  135. Xie W. Ding D. Zi W. Li G. Ma D. Total synthesis and structure assignment of papuamide B, a potent marine cyclodepsipeptide with anti-HIV properties. Angew. Chem. Int. Ed. 2008 47 15 2844 2848 10.1002/anie.200705557 18318032
    [Google Scholar]
  136. Tan L. Ma D. Total synthesis of salinamide A: A potent anti-inflammatory bicyclic depsipeptide. Angew. Chem. Int. Ed. 2008 47 19 3614 3617 10.1002/anie.200800397 18383490
    [Google Scholar]
  137. Waldmann H. Hu T.S. Renner S. Menninger S. Tannert R. Oda T. Arndt H.D. Total synthesis of chondramide C and its binding mode to F-actin. Angew. Chem. Int. Ed. 2008 47 34 6473 6477 10.1002/anie.200801010 18624308
    [Google Scholar]
  138. Li W. Gan J. Ma D. Total synthesis of piperazimycin A: A cytotoxic cyclic hexadepsipeptide. Angew. Chem. Int. Ed. 2009 48 47 8891 8895 10.1002/anie.200904603 19839021
    [Google Scholar]
  139. Li W. Schlecker A. Ma D. Total synthesis of antimicrobial and antitumor cyclic depsipeptides. Chem. Commun. 2010 46 30 5403 5420 10.1039/c0cc00629g 20544117
    [Google Scholar]
  140. Dawson P.E. Muir T.W. Clark-Lewis I. Kent S.B.H. Synthesis of proteins by native chemical ligation. Science 1994 266 5186 776 779 10.1126/science.7973629 7973629
    [Google Scholar]
  141. Tam J.P. Lu Y.A. Liu C.F. Shao J. Peptide synthesis using unprotected peptides through orthogonal coupling methods. Proc. Natl. Acad. Sci. USA 1995 92 26 12485 12489 10.1073/pnas.92.26.12485 8618926
    [Google Scholar]
  142. Shao Y. Lu W. Kent S.B.H. A novel method to synthesize cyclic peptides. Tetrahedron Lett. 1998 39 23 3911 3914 10.1016/S0040‑4039(98)00725‑4
    [Google Scholar]
  143. Tam J.P. Lu Y.A. Yu Q. Thia zip reaction for synthesis of large cyclic peptides: Mechanisms and applications. J. Am. Chem. Soc. 1999 121 18 4316 4324 10.1021/ja984480u
    [Google Scholar]
  144. Fang G.M. Li Y.M. Shen F. Huang Y.C. Li J.B. Lin Y. Cui H.K. Liu L. Protein chemical synthesis by ligation of peptide hydrazides. Angew. Chem. Int. Ed. 2011 50 33 7645 7649 10.1002/anie.201100996 21648030
    [Google Scholar]
  145. Kleineweischede R. Hackenberger C.P.R. Chemoselective peptide cyclization by traceless Staudinger ligation. Angew. Chem. Int. Ed. 2008 47 32 5984 5988 10.1002/anie.200801514 18604792
    [Google Scholar]
  146. Zhao X. Yeung C.S. Dong V.M. Palladium-catalyzed ortho-arylation of O-phenylcarbamates with simple arenes and sodium persulfate. J. Am. Chem. Soc. 2010 132 16 5837 5844 10.1021/ja100783c 20359220
    [Google Scholar]
  147. Fukuzumi T. Ju L. Bode J.W. Chemoselective cyclization of unprotected linear peptides by α-ketoacid–hydroxylamine amide-ligation. Org. Biomol. Chem. 2012 10 30 5837 5844 10.1039/c2ob25129a 22426859
    [Google Scholar]
  148. Li X. Lam H.Y. Zhang Y. Chan C.K. Salicylaldehyde ester-induced chemoselective peptide ligations: Enabling generation of natural peptidic linkages at the serine/threonine sites. Org. Lett. 2010 12 8 1724 1727 10.1021/ol1003109 20232847
    [Google Scholar]
  149. Kleijn L.H.J. Müskens F.M. Oppedijk S.F. de Bruin G. Martin N.I. A concise preparation of the non-proteinogenic amino acid l-kynurenine. Tetrahedron Lett. 2012 53 47 6430 6432 10.1016/j.tetlet.2012.09.055
    [Google Scholar]
  150. Ross F.C. Botting N.P. Leeson P.D. Two syntheses of 2S-[2-2H]-kynurenine. Bioorg. Med. Chem. Lett. 1996 6 7 875 878 10.1016/0960‑894X(96)00128‑X
    [Google Scholar]
  151. Maitrani C. Heyes D.J. Hay S. Arumugam S. Popik V.V. Phillips R.S. Preparation and photophysical properties of a caged kynurenine. Bioorg. Med. Chem. Lett. 2012 22 8 2734 2737 10.1016/j.bmcl.2012.02.097 22444682
    [Google Scholar]
  152. Lohani C.R. Taylor R. Palmer M. Taylor S.D. Solid-phase total synthesis of daptomycin and analogs. Org. Lett. 2015 17 3 748 751 10.1021/acs.orglett.5b00043 25634084
    [Google Scholar]
  153. Moreira R. Wolfe J. Taylor S.D. A high-yielding solid-phase total synthesis of daptomycin using a Fmoc SPPS stable kynurenine synthon. Org. Biomol. Chem. 2021 19 14 3144 3153 10.1039/D0OB02504F 33508054
    [Google Scholar]
  154. Mupparapu N. Lin Y.H.C. Kim T.H. Elshahawi S.I. Regiospecific synthesis of calcium‐independent daptomycin antibiotics using a chemoenzymatic method. Chemistry 2021 27 12 4176 4182 10.1002/chem.202005100 33244806
    [Google Scholar]
  155. Cancer Research UK Abiraterone (Zytiga). Available from: https://www.cancerresearchuk.org/about-cancer/treatment/drugs/abiraterone
  156. Goldberg T. Berrios-Colon E. Abiraterone (zytiga), a novel agent for the management of castration-resistant prostate cancer. P&T 2013 38 1 23 26 23599666
    [Google Scholar]
  157. Abiraterone. Available from: https://medlineplus.gov/druginfo/meds/a611046.html
  158. Padmanabha V. Hariharan K. Demography and disease characteristics of prostate cancer in India. Indian J. Urol. 2016 32 2 103 108 10.4103/0970‑1591.174774 27127351
    [Google Scholar]
  159. Cytecare Hospitals Pvt Prostate cancer: The leading cancer in India. Available from: https://cytecare.com/blog/prostate-cancer/prostate-cancer-the-leading-cancer-in-india/
  160. Madhra M.K. Sriram H.M. Inamdar M. Sharma M.K. Prasad M. Joseph S. Improved procedure for preparation of abiraterone acetate. Org. Process Res. Dev. 2014 18 4 555 558 10.1021/op500044p
    [Google Scholar]
  161. Agrawal A. Kerndt C.C. Manna B. Apixaban. StatPearls StatPearls Publishing Treasure Island (FL) 2024
    [Google Scholar]
  162. Volza Grow Global India apixaban imports: Overview. Available from: https://www.volza.com/p/apixaban/import/import-in-india/
  163. The Hindu Bureau AstraZeneca gets CDSCO nod to import and market critical anti-bleeding drug in India. 2024 Available from: https://www.thehindu.com/news/national/karnataka/astrazeneca-gets-cdsco-nod-to-import-and-market-critical-anti-bleeding-drug-in-india/article67769862.ece
  164. Zhou J. Oh L.M. Philip M. Li H-Y. Confalone P. Synthesis of 4,5-dihydro-pyrazolo [3,4-c] pyrid-2-ones. Patent US6919451B2, 2005
  165. Pinto D.J.P. Orwat M.J. Koch S. Rossi K.A. Alexander R.S. Smallwood A. Wong P.C. Rendina A.R. Luettgen J.M. Knabb R.M. He K. Xin B. Wexler R.R. Lam P.Y.S. Discovery of 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide (apixaban, BMS-562247), a highly potent, selective, efficacious, and orally bioavailable inhibitor of blood coagulation factor Xa. J. Med. Chem. 2007 50 22 5339 5356 10.1021/jm070245n 17914785
    [Google Scholar]
  166. Gant T.G. Shahbaz M.M. Pyrazole carboxamide inhibitors of factor xa. Patent US6919451B2, 2010
  167. Zhou L-L. Zhang X-H. Wu S-K. Hydrazone compounds used as sensor for detection of anions. Acta Chimi. Sin. 2003 61 9 1508 1510
    [Google Scholar]
  168. Jiang J. Ji Y. Alternate synthesis of apixaban (BMS-562247), an inhibitor of blood coagulation factor Xa. Synth. Commun. 2013 43 1 72 79 10.1080/00397911.2011.591956
    [Google Scholar]
  169. Haddaway N.R. Page M.J. Pritchard C.C. PRISMA2020: An R package and Shiny app for producing PRISMA 2020- compliant flow diagrams, with interactivity for optimised digital transparency and Open Synthesis. Campbell System. Rev. 2022 18 e1230
    [Google Scholar]
/content/journals/mroc/10.2174/0118756298319158250227113813
Loading
/content/journals/mroc/10.2174/0118756298319158250227113813
Loading

Data & Media loading...

Supplements

PRISMA checklist is available as supplementary material on the publisher’s website along with the published article.

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test