Abstract
D-Amino acids (D-AAs) have become indispensable building blocks in modern peptide drug design. Although relatively rare in higher organisms, D-AAs are widely utilized in nature, particularly in bacterial peptidoglycans and microbial antimicrobial peptides, where they confer proteolytic stability and unique biological activities. Inspired by these natural strategies, medicinal chemists have successfully incorporated D-Aas into synthetic peptides to overcome the inherent limitations of conventional peptide therapeutics, such as rapid enzymatic degradation and poor bioavailability. The incorporation of D-AAs offers several key advantages, including dramatically enhanced proteolytic resistance, prolonged plasma half-life, reduced immunogenicity, and improved receptor selectivity. These properties have enabled the development of clinically successful drugs across multiple therapeutic areas. Prominent examples include the early antibiotic gramicidin D (1955), the immunosuppressive agent cyclosporine, D-penicillamine, daptomycin, etelcalcetide, difelikefalin, and voclosporin. These compounds illustrate the transformative impact of D-AAs on peptide pharmacology and their expanding role in treating infectious diseases, autoimmune disorders, nephrological conditions, and beyond.
This review highlights the strategic importance of D-AAs in pharmaceutical design, their natural occurrence, clinical applications, and major advances in synthetic methodologies, with particular emphasis on the versatile Ni(II) Schiff base complex approach for the preparation of tailor-made D-AAs. The evolution of D-AA-containing pharmaceuticals demonstrates how stereochemical engineering continues to drive innovation in peptide drug discovery and development.
References
[1] Daniel I., Oger P., Winter R. Origins of life and biochemistry under high-pressure conditions. Chem. Soc. Rev. 2006. 35(10): 858–875.
https://doi.org/10.1039/b517766a .
[2] Fujii N., Saito T. Homochirality and life. Chem. Rec. 2004. 4(5): 267–278.
https://doi.org/10.1002/tcr.20020 .
[3] Meierhenrich U.J. Amino acids and the asymmetry of life. Europ. Rev. 2013. 21(2): 190–199.
https://doi.org/10.1017/S106279871200035X.
[4] Keszthelyi L. Origin of the homochirality of biomolecules. Quart. Rev. Bioph. 1995. 28(4): 473–507.
https://doi.org/10.1017/S0033583500003309.
[5] Shepherd N.E., Hoang H.N., Abbenante G., Fairlie D.P. Left-and right-handed alpha-he¬lical turns in homo-and hetero-chiral helical scaffolds. J. Am. Chem. Soc. 2009. 131(43): 15877–15886.
https://doi.org/10.1021/ja9065283 .
[6] Mazzier D., De S., Wicher B. et al. Parallel Homo¬chiral and Anti‐Parallel Heterochiral Hydrogen‐Bonding Interfaces in Multi‐Helical Abiotic Foldamers. Angew. Chem. In. Ed. 2020. 59(4): 1606–1610.
https://doi.org/10.1002/anie.201912805 .
[7] Hazari A., Sawaya M.R., Vlahakis N et al. The rippled β-sheet layer configuration — a novel supramolecular architecture based on predictions by Pauling and Corey. Chem. Scien. 2022. 13(31): 8947–8952.
https://doi.org/10.1039/D2SC02531K .
[8] Ikai T., Shimizu S., Awata S., Shinohara K.I. Chiral Amplification in π-Conjugated Helical Polymers with Circularly Polarized Luminescence. Macromol. 2018. 51(6): 2328–2334.
https://doi.org/10.1021/acs.macromol.8b0 0229 .
[9] Maeda K., Yashima E. Dynamic Helical Structures: Detection and Amplification of Chira¬lity. In: Crego-Calama, M., Reinhoudt, D.N. (eds) Supramolecular Chirality. Topics in Current Chemistry, vol 265. Springer, Berlin, Heidelberg. 2006 Mar 9:47–88.
https://doi.org/10.1007/128_035 .
[10] Sorochinsky A.E., Soloshonok V.A. Self-disproportionation of Enantiomers of Enantiomerically Enriched Compounds. In: Schurig, V. (eds) Differentiation of Enantiomers II. Topics in Current Chemistry, vol 341. Sprin¬ger, Cham. 2013 Apr 19:301–339.
https://doi.org/10.1007/128_2013_434 .
[11] Han J., Wzorek A., Klika K.D., Soloshonok V.A. Recommended tests for the self-disproportionation of enantiomers (SDE) to ensure accurate reporting of the stereochemical outcome of enantioselective reactions. Molecules. 2021. 26(9): 2757.
https://doi.org/10.3390/molecules26092757.
[12] Han J., Wzorek A., Soloshonok V.A., Klika K.D. The self‐disproportionation of enantio¬mers (SDE): The effect of scaling down, potential problems versus prospective applications, possible new occurrences, and unrealized opportunities? Electrophoresis. 2019. 40(15): 1869–1880.
https://doi.org/10.1002/elps.201800414 .
[13] Du Y., Bian Y., Baecker D. et al. Fluorine in the Pharmaceutical Industry: FDA-Approved Fluorine-Containing Drugs in 2024. Chem. Eur. J. 2025. e202500662.
https://doi.org/10.1002/chem.202500662 .
[14] Wang Q., Bian Y., Dhawan G. et al. FDA approved fluorine-containing drugs in 2023. Chin. Chem. Lett. 2024. 35(11): 109780.
https://doi.org/10.1016/j.cclet.2024.109780 .
[15] Han J., Wzorek A., OnoT. et al. Modern pharmaceutical drugs featuring aliphatic fluorine-containing groups. Ukr. Chem. J. 2025. 91(6): 15–54.
https://doi.org/10.33609/2708-129X.91.6. 2025.15-54 .
[16] Han J., Wzorek A., Dhawan G. et al. Chiral, Fluorine-containing Pharmaceuticals. Ukr. Chem. J. 2025. 91(2): 55–90.
https://doi.org/10.33609/2708-129X.91.2. 2025.55-90 .
[17] Wzorek A., Han J., Ono T. et al. Synthesis of Tailor-Made Amino Acids Containing C(sp2)–F bonds. Ukr. Chem. J. 2025. 91(8): 36–64.
https://doi.org/10.33609/2708-129X.91.8. 2025.36-64 .
[18] Kawai M., Nagai U. Comparison of conformation and antimicrobial activity of synthetic analogs of gramicidin S: Stereochemical consideration of the role of D‐phenylalanine in the antibiotic. Biopol. Orig. Res. Biomol. 1978. 17(6): 1549–1565.
https://doi.org/10.1002/bip.1978.360170613 .
[19] Řeháček Z., De-xiu Z. The biochemistry of cyclosporin formation: a review. Proc. Biochem. 1991. 26(3): 157–166.
doi.org/10.1016/0032-9592(91)80012-E.
[20] Abe H., Yoshikawa N., Sarower M.G., Okada S. Physiological function and metabolism of free D-alanine in aquatic animals. Biol. Pharma. Bull. 2005. 28(9): 1571–1577.
https://doi.org/10.1248/bpb.28.1571 .
[21] Armstrong D.W., Berthod A. Occurrence of D-¬amino acids in natural products. Nat. Prod. Bioprospec. 2023. 13(1): 47.
https://doi.org/10.1007/s13659-023-00412-0 .
[22] Fujii N. D-amino acids in living higher orga¬nisms. Orig. Life Evol. Biosph. 2002. 32(2): 103–127.
https://doi.org/10.1023/A:1016031014871 .
[23] MacKay M.A., Kravtsenyuk M., Thomas R. et al. D-Serine: potential therapeutic agent and/or biomarker in schizophrenia and depression? Front. Psych. 2019. 10: 25.
https://doi.org/10.3389/fpsyt.2019.00025 .
[24] Kalíková K., Šlechtová T., Tesařová E. Enantiomeric ratio of amino acids as a tool for determination of aging and disease diagnostics by chromatographic measurement. Separations. 2016. 3(4): 30.
https://doi.org/10.3390/separations3040030.
[25] Marcone G.L., Rosini E., Crespi E., Pollegioni L. D-amino acids in foods. App. Microbio. Biotech. 2020. 104(2): 555–574.
https://doi.org/10.1007/s00253-019-10264-9.
[26] Liu A., Han J., Nakano A. et al. New pharma¬ceuticals approved by FDA in 2020: Small-¬molecule drugs derived from amino acids and related compounds. Chirality. 2022. 34(1): 86–103.
https://doi.org/10.1002/chir.23376 .
[27] Yin Z., Hu W., Zhang W. et al. Tailor-made amino acid-derived pharmaceuticals appro¬ved by the FDA in 2019. Amino Acids. 2020. 52(9): 1227–1261.
https://doi.org/10.1007/s00726-020-02887-4 .
[28] Liu J., Han J., Izawa K. et al. Cyclic tailor-made amino acids in the design of modern pharmaceuticals. Eur. J. Med. Chem. 2020. 208: 112736.
doi: 10.1016/j.ejmech.2020.112736.
[29] Han J., Konno H., Sato T. et al. Tailor-made amino acids in the design of small-molecule blockbuster drugs. Eur. J. Med. Chem. 2021. 220: 113448.
https://doi.org/10.1016/j.ejmech.2021.1134 48.
[30] Han J., Konno H., Sato T. et al. Peptidomimetics and Peptide-Based Blockbuster Drugs. Curr. Org. Chem. 2021. 25(14): 1627–1658. https://doi.org/10.2174/1385272825666210610155047 .
[31] Farhadi T., Hashemian S.M. Computer-¬aided design of amino acid-based therapeutics: A review. Drug Des. Develop. Therapy. 2018. 14: 1239–1254.
https://doi.org/10.2147/DDDT.S159767 .
[32] Sharma K.K., Sharma K., Rao K. et al. Unna¬tural amino acids: strategies, designs, and applications in medicinal chemistry and drug discovery. J. Med. Chem. 2024. 67(22): 19932–1965.
https://doi.org/10.1021/acs.jmedchem.4c00 110 .
[33] Vig B.S., Huttunen K.M., Laine K., Rautio J. Amino acids as promoieties in prodrug design and development. Adv. Drug Del. Rev. 2013. 65(10): 1370–1385.
https://doi.org/10.1016/j.addr.2012.10.001 .
[34] Wang Q., Han J., Sorochinsky A. et al. The Latest FDA-Approved Pharmaceuticals Containing Fragments of Tailor-Made Amino Acids and Fluorine, Pharmaceuticals. 2022. 15: 999.
https://doi.org/10.3390/ ph15080999 .
[35] Wang N., Mei H., Dhawan G. et al. New Approved Drugs Appearing in the Pharmaceutical Market in 2022, Featuring Fragments of Tailor-Made Amino Acids and Fluorine, Molecules. 2023. 28: 3651.
https://doi.org/10.3390/molecules28093651.
[36] Han J., Wzorek A. Dhawan G. et al. New drugs on the pharmaceutical market containing fluorine and residues of tailor-made amino acids. Ukr. Chem. J. 2024. 90(9): 31–56.
https://doi.org/10.33609/2708-129X.90.9. 2024.31-56.
[37] Han J., Wzorek A., Dhawan G. et al. New drugs appearing on the market in 2023: mole¬cules containing fluorine and fragments of tailor-made amino acids. Ukr. Bioorg. Acta. 2024. 19(1): 3–20.
https://doi.org/10.15407/bioorganica2024.01. 003.
[38] Yu Y., Liu A., Dhawan G. et al. Fluorine-containing pharmaceuticals approved by the FDA in 2020: Synthesis and biological activity. Chin. Chem. Lett. 2021. 32(11): 3342–3354.
https://doi.org/10.1016/j.cclet.2021.05.042 .
[39] Wang Q., Bian Y., Abouchabaka E. et al. Fluo¬rine-containing drugs approved by the US FDA in 2025. Chin. Chem. Lett. 2026. 20: 112640.
https://doi.org/10.1016/j.cclet.2026.112640 .
[40] Bomb K., Zhang Q., Ford E.M. et al. Systematic d-amino acid substitutions to control peptide and hydrogel degradation in cellular microenvironments. ACS Macro Lett. 2023. 12(6): 725–732.
https://doi.org/10.1021/acsmacrolett.3c00 144.
[41] Soloshonok V.A., Kirilenko A.G., Fokina N.A. et al. Biocatalytic Resolution of b-Fluoroalkyl-b-Amino Acids, Tetrahedron: Asym. 1994. 5. 1119–1126.
https://doi.org/10.1016/0957-4166(94)80063-4.
[42] Rezende S.B., Oshiro K.G., Júnior N.G. et al. Advances on chemically modified antimicrobial peptides for generating peptide antibiotics. Chem. Commun. 2021. 57(88): 11578–11590.
https://doi.org/10.1039/d1cc03793e .
[43] Rai J. Peptide and protein mimetics by retro and retroinverso analogs. Chem. Biol. Drug Des. 2019. 93(5): 724–736.
https://doi.org/10.1111/cbdd.13472 .
[44] Pohl E.H., Heine A.N., Sheldrick G.M. et al. Structure of octreotide, a somatostatin analogue. Biol. Crystal. 1995. 51(1): 48–59.
https://doi.org/10.1107/S0907444994006104 .
[45] Sabatine M.S. PCSK9 inhibitors: clinical evi¬dence and implementation. Nature Rev. Cardiol. 2019. 16(3): 155–165. https://doi.org/10.1038/s41569-018-0107-8 .
[46] Chen S., Gfeller D., Buth S.A. et al. Impro¬ving binding affinity and stability of peptide ligands by substituting glycines with d‐amino acids. Chembiochem. 2013. 14(11): 1316–1322.
https://doi.org/10.1002/cbic.201300228.
[47] Sugio S., Petsko G.A., Manning J.M. et al. Crystal structure of a D-amino acid amino¬transferase: how the protein controls stereo¬selectivity. Biochemistry. 1995. 34(30): 9661–9669.
https://doi.org/10.1021/bi00030a002 .
[48] Krishnamoorthy G., Selvakumar R., Sastry T.P. et al. Effect of D-amino acids on collagen fibrillar assembly and stability: Experimental and modelling studies. Biochem. Eng. J. 2013. 75: 92–100.
https://doi.org/10.1016/j.bej.2013.04.002 .
[49] Seia M., Zisman E. Different roles of D‐amino acids in immune phenomena. FASEB J. 1997. 11(6): 449–456.
https://doi.org/10.1096/fasebj.11.6.9194525 .
[50] Li H., Anuwongcharoen N., Malik A.A. et al. Roles of d-amino acids on the bioactivity of host defense peptides. Int. J. Mol. Scien. 2016. 17(7): 1023.
https://doi.org/10.3390/ijms17071023 .
[51] Sanchez Jr. C.J., Akers K.S., Romano D.R. et al. D-amino acids enhance the activity of antimicrobials against biofilms of clinical wound isolates of Staphylococcus aureus and Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 2014. 58(8): 4353–4361.
https://doi.org/10.1128/aac.02468-14 .
[52] Caldwell M., Hughes M., Wei F. et al. Promising applications of D-amino acids in periprosthetic joint infection. Bone Res. 2023. 11(1): 14.
https://doi.org/10.1038/s41413-023-00254-z .
[53] Shi Y., Hussain Z., Zhao Y. Promising application of D-amino acids toward clinical therapy. Int. J. Mol. Scien. 2022. 23(18): 10794.
https://doi.org/10.3390/ijms231810794 .
[54] Sasabe J., Suzuki M.. Emerging role of D-amino acid metabolism in the innate defense. Front. Microbiol. 2018. 9: 933.
https://doi.org/10.3389/fmicb.2018.00933 .
[55] Ravibaskar K., Ganguly A., Roy Barman S. From Amino Acids to Proteins: Biomolecular Nanostructures as Closed-Loop Platforms for Tissue Engineering and Drug Delivery. ACS Nanoscien. Au. 2025. 6(1): 1–20.
https://doi.org/10.1021/acsnanoscienceau.5c 00108 .
[56] Chen M., Zhang S., He Z. Controlled block polypeptide composed of d-type amino acids: a therapeutics delivery platform to inhibit bio¬film formation of drug-resistant bacteria. ACS App. Biomater. 2020. 3(9): 6343–6350. https://doi.org/10.1021/acsabm.0c00795 .
[57] Takada Y., Itoh H., Paudel A. et al. Discovery of gramicidin A analogues with altered acti¬vi¬ties by multidimensional screening of a one-bead-one-compound library. Nature Commun. 2020. 11(1): 4935.
https://doi.org/10.1038/s41467-020-18711-2 .
[58] Andersen O.S. Gramicidin channels. Ann. Rev. Physiol. 1984. 46(1): 531–548.
https://doi.org/10.1146/annurev.ph.46.03 0184.002531 .
[59] Guan Q., Huang S., Jin Y. et al. Recent advances in the exploration of therapeutic analogues of gramicidin S, an old but still potent antimicrobial peptide. J Med. Chem. 2019. 62(17): 7603–7617.
https://doi.org/10.1021/acs.jmedchem.9b0 0156 .
[60] Durand G.A., Raoult D., Dubourg G. Antibiotic discovery: history, methods and perspectives. Int. J. Antimicrob. Agents. 2019. 53(4): 371–382.
https://doi.org/10.1016/j.ijantimicag.2018.11. 010 .
[61] Pavithrra G., Rajasekaran R. Gramicidin peptide to combat antibiotic resistance: a review. Int. J. Pep. Res. Therap. 2020. 26(1): 191–199.
https://doi.org/10.1007/s10989-019-09828-0.
[62] Blanch H.W., Rogers P.L. Optimal conditions for gramicidin S production in continuous cu¬lture. Biotech. Bioengineer. 1972. 14(2): 151–171.
https://doi.org/10.1002/bit.260140202.
[63] Das P., Delost M.D., Qureshi M.H. et al. A survey of the structures of US FDA approved combination drugs. J. Med. Chem. 2018. 62(9): 4265–4311.
https://doi.org/10.1021/acs.jmedchem.8b01 610.
[64] Tedesco D., Haragsim L. Cyclosporine: a review. J. Transplant. 2012. 230386.
https://doi.org/10.1155/2012/230386.
[65] Kahan B.D. Cyclosporine. New Eng. J. Med. 1989. 321(25): 1725–1738.
https://doi.org/10.1056/NEJM19891221321 2507.
[66] Ptachcinski R.J., Burckart G.J., Venkataramanan R. Cyclosporine. Drug Intell. Clin. Pharm. 1985. 19(2): 90–100.
https://doi.org/10.1177/106002808501900202.
[67] Nussenblatt R.B., Palestine A.G. Cyclosporine: immunology, pharmacology and therapeutic uses. Survey Ophthalmol. 1986. 31(3): 159–169. https://doi.org/10.1016/0039-6257(86)90035-4.
[68] Borel J.F., Kis Z.L., Beveridge T. The history of the discovery and development of cyclosporine (Sandimmune®). The search for anti-¬inflammatory drugs: Case His. Con. Clin. 1995. 27–63.
https://doi.org/10.1007/978-1-4615-9846-6_2.
[69] Patocka J., Nepovimova E., Kuca K., Wu W. Cyclosporine A: chemistry and toxicity–a review. Cur. Med. Chem. 2021. 28(20): 3925–3934.
https://doi.org/10.2174/0929867327666201006153202.
[70] Bennett W.M., Norman D.J. Action and toxi¬city of cyclosporine. Ann. Rev. Med. 1986. 37: 215–224.
https://doi.org/10.1146/annurev.me.37.0201 86.001243.
[71] Weigert W.M., Offermanns H., Degussa P.S. D‐Penicillamine—Production and Properties. Angew. Chem. Int. Ed. Eng. 1975. 14(5): 330–336.
https://doi.org/10.1002/anie.197503301.
[72] Van de Stadt R.J., Muijsers A.O., Henrichs A.M., Van der Korst J.K. D-penicillamine: biochemical, metabolic and pharmacological aspects. Scandin. J. Rheumatol. 1979. 8: 13–20.
https://doi.org/10.3109/03009747909108229.
[73] Epstein O., Lee R., Boss A.M. et al. D-penicillamine treatment improves survival in primary biliary cirrhosis. Lancet. 1981. 317(8233): 1275–1277.
https://doi.org/10.1016/S0140-6736(81)924 56-9.
[74] Perrett D. An outline of D-penicillamine metabolism. Proceed. Royal Soc. Med. 1977. 70: 61–64.
https://doi.org/10.1177/00359157770700S321.
[76] Neuberger J., Christensen E., Portmann B. et al. Double-blind controlled trial of d-penicill¬amine in patients with primary biliary cirrhosis. Gut. 1985. 26(2): 114–119.
https://doi.org/10.1136/gut.26.2.114.
[77] Tedesco K.L., Rybak M.J.. Daptomycin. Pharmacotherapy: J. Hum. Pharm. Drug Ther. 2004. 24(1): 41–57.
https://doi.org/10.1592/phco.24.1.41.34802.
[78] Humphries R.M., Pollett S., Sakoulas G. A current perspective on daptomycin for the clinical microbiologist. Clin. Microb. Rev. 2013. 26(4): 759–780.
https://doi.org/10.1128/cmr.00030-13.
[79] Enoch D.A., Bygott J.M., Daly M.L., Karas J.A. Daptomycin. J. Infec. 2007. 55(3): 205–213.
https://doi.org/10.1016/j.jinf.2007.05.180.
[80] Fenton C., Fenton C., Keating G.M., Curran M.P. Daptomycin. Drugs. 2004. 64(4): 445–455.
https://doi.org/10.2165/00003495-200464040- 00009.
[81] Raja A., LaBonte J., Lebbos J., Kirkpatrick P. Daptomycin. Nature Rev. Drug Dis. 2003. 2(12): 943–944.
https://doi.org/10.1038/nrd1258.
[82] Baltz R.H. Daptomycin: mechanisms of action and resistance, and biosynthetic engineering. Cur. Opin. Chem. Biol. 2009. 13(2): 144–151.
https://doi.org/10.1016/j.cbpa.2009.02.031.
[83] Blair H.A. Etelcalcetide: first global approval. Drugs. 2016. 76(18): 1787–1792.
https://doi.org/10.1007/s40265-016-0671-3.
[84] Dörr K., Kammer M., Reindl-Schwaighofer R. et al. Randomized trial of etelcalcetide for cardiac hypertrophy in hemodialysis. Circul. Res. 2021. 128(11): 1616–1625.
https://doi.org/10.1161/CIRCRESAHA.120. 318556.
[85] Block G.A., Bushinsky D.A., Cunningham J. et al. Effect of etelcalcetide vs placebo on serum parathyroid hormone in patients recei¬ving hemodialysis with secondary hyperpa¬rathyroidism: two randomized clinical trials. JAMA. 2017. 317(2): 146–155.
https://doi.org/10.1001/jama.2016.19456.
[86] Block G.A., Bushinsky D.A., Cheng S. et al. Effect of etelcalcetide vs cinacalcet on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism: a randomized clinical trial. JAMA. 2017. 317(2): 156–164.
https://doi.org/10.1001/jama.2016.19468.
[87] Yu L., Tomlinson J.E., Alexander S.T. et al. Etelcalcetide, a novel calcimimetic, prevents vascular calcification in a rat model of renal insufficiency with secondary hyperpara¬thyroidism. Cal. Tissue Int. 2017. 101(6): 641–653.
https://doi.org/10.1007/s00223-017-0319-7.
[88] Freitas P., Pereira L. Etelcalcetide: What we know eight years since its approval. Nefrologia. 2025. 45(2): 116–134.
https://doi.org/10.1016/j.nefro.2024.09.004.
[89] Deeks E.D. Difelikefalin: first approval. Drugs. 2021. 81(16): 1937–1944.
https://doi.org/10.1007/s40265-021-01619-6.
[90] Fugal J., Serpa S.M. Difelikefalin: a New κ-Opioid receptor agonist for the treatment of hemodialysis-dependent chronic kidney disease–associated pruritus. Ann. Pharm. 2023. 57(4): 480–488.
https://doi.org/10.1177/10600280221115889.
[91] Cai X., Wu G., Lin Y., Yang L. Difelikefalin in the treatment of hemodialysis patients with pruritus: a systematic review and meta-ana¬lysis. Front. Pharm. 2024. 15: 1476587.
https://doi.org/10.3389/fphar.2024.1476587.
[92] Stark J.G., Noonan P.K., Spencer R.H. et al. Pharmacokinetics, metabolism, and excretion of intravenous [14C] Difelikefalin in healthy subjects and subjects on hemodialysis. Clin. Pharm. 2023. 62(9): 1231.
https://doi.org/10.1007/s40262-023-01262-2.
[93] Spahia N., Rroji M., Mumajesi S. et al. Beyond the itch: chronic kidney disease-associated pruritus, a multimodal approach, and the role of difelikefalin. Arch. Derma. Res. 2024. 317(1): 120.
https://doi.org/10.1007/s00403-024-03640-7.
[94] van Gelder T., Lerma E., Engelke K., Huizinga R.B. Voclosporin: a novel calcineurin inhibitor for the treatment of lupus nephritis. Exp. Rev. Clin. Pharm. 2022. 15(5): 515–529.
https://doi.org/10.1080/17512433.2022.2092470.
[95] Abdel-Kahaar E., Keller F. Clinical pharmacokinetics and pharmacodynamics of voclosporin. Clin. Pharm. 2023. 62(5): 693–703.
https://doi.org/10.1007/s40262-023-01246-2.
[96] Jiang B., Liu J., Li Y. et al. Synthesis and Crystallization Research of Voclosporin. Org. Proc. Res. Develop. 2024. 28(4):1151–1158.
https://doi.org/10.1021/acs.oprd.3c00518.
[97] Li Y., Palmisano M., Sun D., Zhou S. Pharma¬cokinetic disposition difference between cyc¬lo¬sporine and voclosporin drives their distinct efficacy and safety profiles in clini¬cal studies. Clin. Pharm. Adv. App. 2020. 1: 83–96.
https://doi.org/10.2147/CPAA.S255789.
[98] Mejía-Vilet J.M., Romero-Díaz J. Voclospo¬rin: a novel calcineurin inhibitor for the management of lupus nephritis. Exp. Rev. Clin. Immun. 2021, 17(9): 937–945.
https://doi.org/10.1080/1744666X.2021.196 7747.
[99] Najera C., Sansano J.M. Catalytic asymmetric synthesis of α-amino acids. Chem. Rev. 2007. 107(11): 4584–4671.
https://doi.org/10.1021/cr050580o.
[100] Wang Y., Song X., Wang J. et al. Recent approaches for asymmetric synthesis of α-amino acids via homologation of Ni(II) complexes. Amino Acids. 2017. 49(9): 1487–1520.
https://doi.org/10.1007/s00726-017-2458-6.
[101] Zou Y., Han J., Saghyan A.S. et al. Asymmetric Synthesis of Tailor-Made Amino Acids Using Chiral Ni(II)-Complexes of Schiff Bases; An Update of the Recent Literature, Molecules. 2020. 25: 2739.
https://doi.org/10.3390/molecules25122739.
[102] Takeda R., Abe H., Shibata N. et al. Asymmetric synthesis of α-deuterated α-amino acids. Org. Biomol. Chem. 2017. 15(33): 6978–6983.
https://doi.org/10.1039/C7OB01720K.
[103] Sun X.-S., Ou Yang Q., Xu S.-M. et al. Asymmetric synthesis of quaternary α trifluoro¬methyl α amino acids by Ir catalyzed ally¬lation followed by kinetic resolution. Chem. Commun. 2020. 56(22): 3333–3336.
https://doi.org/10.1039/d0cc00845a.
[104] Phillips A.M., Pombeiro A.J. Electrochemical asymmetric synthesis of biologically active substances. Org. Biomol. Chem. 2020. 18(36): 7026–7055.
https://doi.org/10.1039/D0OB01425G.
[105] Yuan T., Tang Q., Radefeld K. et al. Facile Asymmetric Synthesis of α, α-Disubstituted Amino Acid Derivatives with Gold Redox Catalysis Using a Chiral Auxiliary. ACS Cat. 2025. 15(17): 14845–14852.
https://doi.org/10.1021/acscatal.5c02965.
[106] Sato T., Izawa K., Aceña J.L. et al. Tailor-Made α-Amino Acids in Pharmaceutical Industry: Synthetic Approaches to (1R,2S)-1-Amino-2-¬vinylcyclopropane-1-carboxylic Acid (Vinyl-ACCA). Eur. J. Org. Chem. 2016, 2757–2774.
https://doi.org/10.1002/ejoc.201600112.
[107] Turcheniuk K.V., Poliashko K.O., Kukhar V.P. et al. Efficient asymmetric synthesis
of tri¬fluoromethylated β-aminophosphona¬tes and their incorporation into dipeptides. Chem. Commun. 2012. 48(94): 11519–11521.
https://doi.org/10.1039/c2cc36702e.
[108] Soloshonok, V.A.; Ohkura, H.; Yasumoto M. Operationally convenient asymmetric synthesis of (S)- and (R)-3-amino-4,4,4-trifluorobutanoic acid: Part II. Enantioselective biomimetic transamination of 4,4,4-trifluoro-3-oxo-N-[(R)-1-phenylethyl)butanamide. J. Fluor. Chem. 2006. 127(7): 930–935.
https://doi.org/10.1016/j.jfluchem.2006.04. 004.
[109] Dennig A., Blaschke F., Gandomkar S. et al. Preparative asymmetric synthesis of canonical and non‐canonical α‐amino acids through formal enantioselective biocatalytic amination of carboxylic acids. Adv. Syn. Cat. 2019. 361(6): 1348–1358.
https://doi.org/10.1002/adsc.201801377.
[110] Patel RN. Biocatalysis: Synthesis of key intermediates for development of pharmaceuticals. ACS Cat. 2011. 1(9): 1056–1074.
https://doi.org/10.1021/cs200219b.
[111] Wohlgemuth R. Tools and ingredients for the biocatalytic synthesis of metabolites. Bio¬tech. J. 2009. 4(9): 1253–1265,
https://doi.org/10.1002/biot.200900002.
[112] Tomoiaga R.B., Nagy L.C., Boros K. et al. Engineered Biocatalysts for the Asymmetric Synthesis of d-Phenylalanines. ACS Cat. 2025. 15(9): 7361–7389.
https://doi.org/10.1021/acscatal.5c00837.
[113] Petchey M.R., Schneider P., Harwood L.A. Biocatalytic Amino Acid Functionalisation. ChemMedChem. 2025. 20(5): e202400628.
https://doi.org/10.1002/cmdc.202400628.
[114] Soloshonok V.A., Kirilenko A.G., Fokina N.A. et al. Chemo-enzymatic approach to the synthesis of each of the four isomers of α-alkyl-¬β-fluoroalkyl-substituted β-amino acids. Tetrahedron: Asym. 1994. 5(7): 1225–1228.
https://doi.org/10.1016/0957-4166(94)801 63-0.
[115] Soloshonok V.A., Fokina N.A., Rybakova A.V. et al. Biocatalytic Approach to Enantiomerically Pure b-Amino Acids. Tetrahedron: Asym. 1995. 6: 1601–1610.
https://doi.org/10.1016/0957-4166(95)00 204-3.
[116] Pollegioni L., Rosini E., Molla G. Advances in enzymatic synthesis of D-amino acids. Int. J. Mol. Scien. 2020. 21(9): 3206.
https://doi.org/10.3390/ijms21093206.
[117] Wang F., Qi H., Li H. et al. State-of-the-art strategies and research advances for the bio¬synthesis of D-amino acids. Crit. Rev. Biotech. 2024. 44(4): 495–513.
https://doi.org/10.1080/07388551.2023.2193861.
[118] Soloshonok V.A., Soloshonok I.V., Kukhar V.P., Svedas V.K. Biomimetic transamination of α-alkyl β-keto carboxylic esters. Chemoenzymatic approach to the stereochemically defined α-alkyl β-fluoroalkyl β-amino acids. J. Org. Chem. 1998. 63(6): 1878–1884.
https://doi.org/10.1021/jo971777m.
[119] Chakrabarty S., Romero E.O., Pyser J.B. et al. Chemoenzymatic total synthesis of natu¬ral products. Acc. Chem. Res. 2021. 54(6): 1374–1384.
https://doi.org/10.1021/acs.accounts.0c00 810.
[120] Kaspar F., Schallmey A. Chemo-enzyma¬tic synthesis of natural products and their analogs. Curr. Opin. Biotechnol. 2022. 77: 102759.
https://doi.org/10.1016/j.copbio.2022.102 759.
[121] Sorochinsky A.E., Aceña J.L., Moriwaki H. et al. Asymmetric synthesis of α-amino acids via homologation of Ni(II) complexes of glycine Schiff bases; Part 1: Alkyl halide alkylations. Amino Acids. 2013. 45: 691–718.
https://doi.org/10.1007/s00726-013-1539-4.
[122] Sorochinsky A.E., Aceña J.L., Moriwaki H. et al. Asymmetric synthesis of a-amino acids via homologation of Ni(II) complexes of glycine Schiff bases. Part 2: Aldol, Mannich addition reactions, deracemization and (S) to (R) interconversion of a-amino acids. Amino Acids. 2013. 45: 1017–1033.
https://doi.org/10.1007/s00726-013-1580-3.
[123] Aceña J.L., Sorochinsky A.E., Soloshonok V. Asymmetric synthesis of a-amino acids via homologation of Ni(II) complexes of glycine Schiff bases. Part 3: Michael addition reactions and miscellaneous transformations. Amino Acids. 2014. 46: 2047–2073.
https://doi.org/10.1007/s00726-014-1764-5.
[124] Wang J., Lin D., Zhou S. et al. Asymmetric Synthesis of Sterically Constrained Linear Trifluoromethyl Containing Amino Acids via Alkylation of Chiral Equivalents of Nucleo¬philic Glycine and Alanine. J. Org. Chem. 2011. 76: 684–687.
https://doi.org/10.1021/jo102031b.
[125] Tang X., Soloshonok V.A., Hruby V.J. Convenient Asymmetric Synthesis of Enantiomerically Pure 2’,6’-Dimethyltyrosine (DMT) via Alkylation of Chiral Nucleophilic Glycine Equivalent. Tetrahedron: Asym. 2000. 11: 2917–2925.
https://doi.org/10.1016/S0957-4166(00)00 250-0.
[126] Soloshonok V.A., Tang X., Hruby V.J. Large-Scale Asymmetric Synthesis of Novel Steri¬cally Constrained 2’,6’-Dimethyl- and a,2’,6’-¬Trimethyltyrosine and –phenylalanine Derivatives via Alkylation of Chiral Equivalents of Nucleophilic Glycine and Alanine. Tetrahedron. 2001. 57: 6375–6382.
https://doi.org/10.1016/S0040-4020(01)005 04-X.
[127] Ellis T.K., Ueki H., Yamada T. et al. The Design, Synthesis and Evaluation of a New Generation of Modular Nucleophilic Glycine Equivalents for the Efficient Synthesis of Sterically Constrained a-Amino Acids J. Org. Chem. 2006. 71: 8572–8578.
[128] Ellis T.K., Hochla V.M., Soloshonok V.A. Efficient synthesis of 2-aminoindane-2-carboxylic acid via dialkylation of nucleo¬philic glycine equivalent. J. Org. Chem. 2003. 68(12): 4973–4976.
https://doi.org/10.1021/jo030065v.
[129] Ellis T.K., Martin C.H., Ueki H., Soloshonok V.A. Efficient, Practical Synthesis of Symmetrically a,a-Disubstituted a-Amino Acids. Tetrahedron Lett. 2003. 44: 1063–1066.
https://doi.org/10.1016/S0040-4039(02)02719-3.
[130] Ueki H., Ellis, T. K., Martin C.H. Soloshonok V.A. Efficient Large-Scale Synthesis of Picolinic Acid Derived Ni(II)-Complexes of Glycine. Eur. J. Org. Chem. 2003. 1954–1957. https://doi.org/10.1002/ejoc.200200688.
[131] Ellis T.K., Martin C.H., Tsai G.M. et al. Efficient Synthesis of Sterically Constrained Symmetrically a,a-Disubstituted a-Amino Acids under Operationally Convenient Conditions. J. Org. Chem. 2003. 68: 6208–6214.
https://doi.org/10.1021/jo030075w.
[132] Soloshonok V.A., Tang X., Hruby V.J., Meervelt L.V. Asymmetric Synthesis of a,b-¬Dialkyl-a-Phenylalanines via Direct Al¬ky¬la¬tion of Chiral Alanine Derivative with Racemic a-Alkylbenzylbromides. A Case of High Enantiomer Differentiation at Room Temperature. Org. Lett. 2001. 3: 341–343.
https://doi.org/10.1021/ol000330o.
[133] Soloshonok V.A, Boettiger T.U., Bolene S.B. Asymmetric Synthesis of (2S,3S)- and (2R,3R)-a,b-Dialkyl-a-Amino Acids via Al¬kylation of Chiral Ni(II)-Complexes of Aliphatic a-Amino Acids with Racemic a-Alkyl¬benzylbromides. Synthesis. 2008. 2594–2602.
https://doi.org/10.1055/s-2008-1067172.
[134] Taylor S.M., Yamada T., Ueki H., Soloshonok V.A. Asymmetric synthesis of enantiomerically pure 4-aminoglutamic acids via methy¬lenedimerization of chiral glycine equivalents with dichloromethane under operationally convenient conditions. Tetrahedron Lett. 2004. 45(50): 9159–9162.
https://doi.org/10.1016/j.tetlet.2004.10.111.
[135] Wang J., Liu H., Aceña J.L. et al. Synthesis of bis-α,α-amino acids through diastereoselective bis-alkylations of chiral Ni(II)-complexes of glycine. Org. Biomol. Chem. 2013. 11: 4508–4515.
https://doi.org/10.1039/C3OB40594J.
[136] Soloshonok V.A., Kukhar V.P., Galushko S.V. et al. General Method for the Synthesis of Enantiomerically Pure b-Hydroxy-a-Amino Acids, Containing Fluorine Atoms in the Side Chains. Case of Stereochemical Distinction Between Methyl and Trifluoro¬methyl Groups. X-Ray Crystal and Molecular Structure of the Nickel(II) Complex of (2S,3S)-2-(Trifluoromethyl)threonine. J. Chem. Soc. Perkin Trans 1. 1993. 3143–3155.
https://doi.org/10.1039/P19930003143.
[137] Soloshonok V.A., Avilov D.V., Kukhar V.P. Highly Diastereoselective Asymmetric Aldol Reactions of Chiral Ni(II)-Complex of Glycine with Trifluoromethyl Ketones. Tetrahedron: Asym. 1996. 7: 1547–1550.
https://doi.org/10.1016/0957-4166(96)001 77-2.
[138] Soloshonok V.A., Avilov D.V., Kukhar V.P. Asymmetric Aldol Reactions of Trifluoromethyl Ketones with a Chiral Ni(II) Complex of Glycine: Stereocontrolling Effect of the Trifluoromethyl Group. Tetrahedron. 1996. 52: 12433–12442.
https://doi.org/10.1016/0040-4020(96)007 41-7.
[139] Kawamura A., Moriwaki H., Röschenthaler G.-V. et al. Synthesis of (2S,3S)-β-(trifluoromethyl)-α,β-diamino acid by Mannich addition of glycine Schiff base Ni(II) comp¬lexes to N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimine. J. Fluor. Chem. 2015. 171: 67–72.
https://doi.org/10.1016/j.jfluchem.2014.09. 013.
[140] Soloshonok V.A., Avilov D.V., Kukhar V.P. et al. Highly Diastereoselective aza-Aldol Reactions of a Chiral Ni(II) Complex of Glycine with Imines. An Efficient Asymmetric Approach to 3-Perfluoroalkyl-2,3-Diamino Acids. Tetrahedron Lett. 1997. 38: 4671–4674.
https://doi.org/10.1016/S0040-4039(97)009 63-5.
[141] Soloshonok V.A., Cai C., Hruby V.J. A Practical Asymmetric Synthesis of Enantiomerically Pure 3-Substituted Pyroglutamic Acids and Related Compounds. Angew. Chem. Int. Ed. 2000. 39: 2172–2175. Angew. Chem. 2000. 112: 2256–2259.
https://doi.org/10.1002/1521-3757(20000616)
112:12<2256::AID-ANGE2256>3.0.CO;2-9.
[142] Soloshonok V.A., Cai C., Hruby V.J. A Unique Case of Face Diastereoselectivity in the Michael Addition Reactions Between Ni(II)-Complexes of Glycine and Chiral 3-(E-enoyl)-1,3-oxazolidin-2-ones. Tetrahedron Lett. 2000. 41: 9645–9649.
https://doi.org/10.1016/S0040-4039(00)017 37-8.
[143] Soloshonok V.A., Cai C., Hruby V.J. Asymmetric Michael Addition Reactions of Chiral Ni(II) Complex of Glycine with N-(Enoyl)oxazolidinones: Improved Reactivity and Stereochemical Outcome. Tetrahedron: Asym. 1999. 10: 4265–4269.
https://doi.org/10.1016/S0957-4166(99)004 83-8.
[144] Soloshonok V.A., Cai C., Hruby V.J. Toward Design of a Practical Methodology for Stereocontrolled Synthesis of c-Constrained Pyroglutamic Acids and Related Compounds. Virtually Complete Control of Simple Diastereoselectivity in the Michael Addition Reactions of Glycine Ni(II) Complexes with N-(Enoyl)oxazolidinones. Tetrahedron Lett. 2000. 41: 135–139.
https://doi.org/10.1016/S0040-4039(99)02 018-3.
[145] Soloshonok V.A., Ueki H., Ellis T.K. et al. Application of Modular Nucleophilic Glycine Equivalents for Truly Practical Asymmetric Synthesis of b-Substituted Pyroglutamic Acids. Tetrahedron Lett. 2005. 46: 1107–1110.
https://doi.org/10.1016/j.tetlet.2004.12.093.
[146] Soloshonok V.A., Cai C., Hruby V.J. (S)- or (R)-N-(E-enoyl)-4-phenyl-1,3-oxazolidin-2-ones: Ideal Michael Acceptors to Afford a Virtually Complete Control of Simple and Face Diastereoselectivity in Addition Reactions with Glycine Derivatives. Org. Lett. 2000. 2: 747–750.
https://doi.org/10.1021/ol990402f.
[147] Shigeno Y., Han J., Soloshonok V.A. et al. Asymmetric synthesis of (S)-3-methyleneglutamic acid and its N-Fmoc derivative via Michael addition of chiral glycine Schiff base Ni(II) complex with enol tosylates. Chirality. 2021. 33: 115–123.
https://doi.org/doi.org/10.1002/chir.23291.
[148] Cai, C.; Soloshonok, V.A.; Hruby V.J. Michael Addition Reactions between Chiral Ni(II) Complex of Glycine and 3-(trans-Enoyl)oxazolidin-2-ones. A Case of Electron Donor–Acceptor Attractive Interaction-Controlled Face Diastereoselectivity. J. Org. Chem. 2001, 66(4), 1339–1350.
https://doi.org/10.1021/jo0014865.
[149] Soloshonok V.A., Avilov D.V., Kukhar V. P. et al. An Efficient Asymmetric Synthesis of (2S,3S)-3-Trifluoromethylpyroglutamic Acid. Tetrahedron Lett. 1997. 38: 4903–4904.
https://doi.org/10.1016/S0040-4039(97)010 54-X.
[150] Soloshonok V.A., Cai C., Hruby V.J. et al. Rational Design of Highly Diastereoselective, Organic Base-Catalyzed, Room Temperature Michael Addition Reactions. J. Org. Chem. 2000. 65: 6688-6696.
https://doi.org/10.1021/jo0008791.
[151] Cai M., Cai C., Mayorov A.V. et al. Biological and conformational study of b-substituted prolines in MT-II template: steric effects leading to human MC5 receptor selectivity. J. Pep. Res. 2004. 63: 116–131.
https://doi.org/10.1111/j.1399-3011.2003. 00105.x.
[152] Qiu W., Gu X., Soloshonok V.A. et al. Stereoselective synthesis of conformationally constrained reverse turn dipeptide mimetics. Tetrahedron Lett. 2001. 42(2): 145–148.
https://doi.org/10.1016/S0040-4039(00)01 864-5.
[153] Tokunaga E., Akiyama H., Soloshonok V.A. et al. Biological evaluation of both enantiomers of fluoro-thalidomide using human myeloma cell line H929 and others. PLoS ONE. 2017. 12(8): e0182152.
https://doi.org/10.1371/journal.pone.018 2152.
[154] Soloshonok V.A., Yamada T., Sakaguchi K., Ohfune Y. Concise Asymmetric Synthesis of Configurationally Stable 4-trifluoromethyl Thalidomide, Fut. Med. Chem. 2009. 1: 897–908.
https://doi.org/10.4155/fmc.09.63.
[155] Yamada T., Okada T., Sakaguchi K. et al. Efficient Asymmetric Synthesis of Novel 4-Substituted and Configurationally Stable Analogs of Thalidomide. Org. Lett. 2006. 8: 5625–5628.
https://doi.org/10.1021/ol0623668.
[156] Yamada T., Sakaguchi K., Shinada T. et al. Efficient asymmetric synthesis of the functionalized pyroglutamate core unit common to oxazolomycin and neooxazolomycin using Michael reaction of nucleophilic glycine Schiff base with a,b-disubstituted acrylate. Tetrahedron: Asym. 2008. 19: 2789–2795.
https://doi.org/10.1016/j.tetasy.2008.11.036.
[157] Oyama K., Han J., Moriwaki H. et al. Synthesis of Ahod moiety of ralstonin A using amino acid Schiff base Ni(II)-complex chemistry. Helv. Chim. Acta. 2020. 103: e2000077.
https://doi.org/10.1002/hlca.202000077.
[158] Kawashima A., Shu S., Takeda R. et al. Advanced asymmetric synthesis of (1R,2S)-¬1-amino-2-vinylcyclopropanecarboxylic acid by alkylation/cyclization of newly designed axially chiral Ni(II) complex of glycine Schiff base. Amino Acids. 2016. 48: 973–986.
https://doi.org/10.1007/s00726-015-2138-3.
[159] Kawashima A., Xie C., Mei H. et al. Soloshonok, Asymmetric synthesis of (1R,2S)-¬1-amino-2-vinylcyclopropanecarboxylic acid by sequential SN2–SN2’ dialkylation of (R)-N-¬(benzyl)proline-derived glycine Schiff base Ni(II) complex, RSC Adv. 2015. 5: 1051–1058.
https://doi.org/10.1039/C4RA12658K.
[160] Wzorek A., Han J., Ono T. et al. Cutting-Edge Strategies in the Asymmetric Synthesis of α-Aminocyclopropyl Carboxylic Acids: Essential Scaffolds for Drug Discovery. Ukr. Chem. J. 2025. 91(10): 27–71.
https://doi.org/10.33609/2708-129X.91.10. 2025.27-71.
[161] Ueki H., Ellis T.K., Martin C.H. et al. Improved Synthesis of Proline Derived Ni(II)-¬Complexes of Glycine, a Versatile Chiral Equivalents of Nucleophilic Glycine for General Asymmetric Synthesis of a-Amino Acids. J. Org. Chem. 2003. 68: 7104–7107.
https://doi.org/10.1021/jo0301494.
[162] Soloshonok V.A., Ueki H., Ellis T.K. New Generation of Nucleophilic Glycine Equivalents. Tetrahedron Lett. 2005. 46: 941–944.
https://doi.org/10.1016/j.tetlet.2004.12.093.
[163] Soloshonok V.A., Ueki H., Moore J.L., Ellis T.K. Design and Synthesis of Molecules with Switchable Chirality via Formation and Cleavage of Metal-Ligand Coordination Bonds, J. Am. Chem. Soc. 2007. 129: 3512–3513.
https://doi.org/10.1021/ja067995r.
[164] Han J., Romoff T.T., Moriwaki H.H. et al. Development of Hamari Ligands for Practical Asymmetric Synthesis of Tailor-¬Made Amino Acids. ACS Omega. 2019. 4: 18942−18947.
https://doi.org/10.1021/acsomega.9b02940.
[165] Mei H., Han J., Takeda R. et al. Practical Method for Preparation of (S) 2-Amino-¬5,5,5-trifluoropentanoic Acid via Dyna¬mic Kinetic Resolution. ACS Omega. 2019. 4: 11844−11851.
https://doi.org/10.1021/acsomega.9b01537.
[166] Han J., Liu H., Wang J. et al. Hamari’s contribution to the asymmetric synthesis of tailor-made amino acids. Ukr. Chem. J. 2024. 90(10): 88–134.
https://doi.org/10.33609/2708-129X.90.10. 2024.88-134.
[167] Jörres M., Aceña J.L., Soloshonok V.A., Bolm C. Asymmetric Carbon-Carbon Bond Formations under Solvent-Less Conditions in Ball Mills. ChemCatChem. 2015. 7: 1265–1269.
https://doi.org/10.1002/cctc.201500102.
[168] Jörres M., Chen X., Aceña J.L. et al. Asymmetric Synthesis of a-Amino Acids under Operationally Convenient Conditions. Adv. Synth. Catal. 2014. 356: 2203–2208.
https://doi.org/10.1002/adsc.201400405.
[169] Bergagnini M., Fukushi K., Han J. et al. NH-type of chiral Ni(II) complexes of glycine Schiff base: design, structural evaluation, reactivity and synthetic applications. Org. Biomol. Chem. 2014. 12: 1278–1291.
https://doi.org/10.1039/C3OB41959B.
[170] Takeda R., Kawamura A., Kawashima A. et al. Second-order asymmetric transformation and its application for the practical synthesis of α-amino acids. Org. Biomol. Chem. 2018. 16: 4968–4972.
https://doi.org/10.1039/C8OB00963E.
[171] Soloshonok V.A., Ellis T.K. Design and Synthesis of a New Generation of “NH” Ni(II) Complexes of Glycine Schiff Bases and Their Unprecedented C-H vs. N-H Chemoselectivity in the Alkyl Halide Alkylations and Michael addition Reactions. Synlett. 2006. 533–538.
https://doi.org/10.1055/s-2006-926252.
[172] Romoff T.T., Palmer A.B., Mansour N. et al. Scale-up Synthesis of (R)- and (S)-N-(2-benzoyl-4-chlorophenyl)-1-(3,4-dichlorobenzyl)pyrrolidine-2-carboxamide hydrochloride, a Versatile Reagent for Preparation of Tailor-made α- and β-Amino Acids in Enantiomerically Pure Form. Org. Process Res. Dev. 2017. 21: 732−739.
https://doi.org/10.1021/acs.oprd.7b00055.
[173] Romoff T.T., Ignacio B.G., Mansour N. et al. Large-Scale Synthesis of the Glycine Schiff Base Ni(II) Complex Derived from (S)- and (R) N (2-Benzoyl-4-chloro¬phenyl)-1-[(3,4dichlorophenyl)methyl]-2-pyrrolidinecarboxamide. Org. Process Res. Dev. 2020. 24: 294−300.
https://doi.org/10.1021/acs.oprd.9b00399.
[174] Nian Y., Wang J., Moriwaki H. et al. Ana¬lysis of crystallographic structures of Ni(II) complexes of α-amino acid Schiff bases; Elucidation of the substituents effect on stereochemical preferences Dalton Trans. 2017. 46: 4191–4198.
https://doi.org/10.1039/C7DT00014F.
[175] Nian Y., Wang J., Zhou S. et al. Recyclable Ligands for the Non-Enzymatic Dynamic Kinetic Resolution of Challenging a-Amino Acids. Angew. Chem. Int. Ed. 2015. 54: 12918-12922.
https://doi.org/10.1002/anie.201507273.
[176] Wang S., Zhou S., Wang J. et al. Chemical Dynamic Thermodynamic Resolution and S/R Interconversion of Unprotected Unnatural Tailor-made a-Amino Acids. J. Org. Chem. 2015. 80: 9817–9830.
https://doi.org/10.1021/acs.joc.5b01292.
[177] Takeda R., Kawamura A., Kawashima A. et al. Chemical Dynamic Kinetic Resolution and (S)/(R)-Interconversion of Unprotected α-Amino Acids. Angew. Chem. Int. Ed. 2014. 53: 12214–12217.
https://doi.org/10.1002/anie.201407944.
[178] Soloshonok V.A., Ellis T.K., Ueki H., Ono T. Resolution/Deracemization of Chiral a-Ami¬no Acids Using Resolving Reagents with Flexible Stereogenic Centers. J. Am. Chem. Soc. 2009. 131: 7208-7209.
https://doi.org/10.1021/ja9026055.
[179] Zhou S., Wang J., Chen X. et al. Chemical Kinetic Resolution of Unprotected b-Substituted-b-Amino Acids Using Recyclable Chiral Ligands. Angew. Chem. Int. Ed. 2014. 53: 7883–7886.
https://doi.org/10.1002/anie.201403556.
[180] Sorochinsky A.E., Ueki H., Aceña J.L. et al. Chemical approach for interconversion of (S)- and (R)-α-amino acids. Org. Biomol. Chem. 2013. 11: 4503–4507.
https://doi.org/10.1039/C3OB40541A.
[181] Nian Y., Wang J., Zhou S. et al. Purely Chemical Approach for Preparation of D-alpha-amino Acids via (S)-to-(R)-interconversion of Unprotected Tailor-made alpha-amino Acids. J. Org. Chem. 2016. 81: 3501–3508.
https://doi.org/10.1021/acs.joc.5b02707.
[182] Sorochinsky A.E., Ueki H., Aceña J.L. et al. Chemical deracemization and (S) to (R) interconversion of some fluorine-containing α-amino acids. J. Fluor. Chem. 2013. 152: 114–118.
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