Enzyme- and Chemo-enzyme-Catalyzed Stereodivergent Synthesis

 

 Permissions and Reprints

Abstract

Multiple stereoisomers can be found when a substance contains chiral carbons in its chemical structure. To obtain the desired stereoisomers, asymmetric synthesis was proposed in the 1970s and developed rapidly at the beginning of this century. Stereodivergent synthesis, an extension of asymmetric synthesis in organic synthesis with the hope to produce all stereoisomers of chiral substances in high conversion and selectivity, enriches the variety of available products and serves as a reference suggestion for the synthesis of their derivatives and other compounds. Since biocatalysis has outstanding advantages of economy, environmental friendliness, high efficiency, and reaction at mild conditions, the biocatalytic reaction is regarded as an efficient strategy to perform stereodivergent synthesis. Thus, in this review, we summarize the stereodivergent synthesis catalyzed by enzymes or chemo-enzymes in cases where a compound contains two or three chiral carbons, i.e., at most four or eight stereoisomers are present. The types of reactions, including reduction of substituent ketones, cyclization reactions, olefin addition, and nonredox transesterification reactions, are also discussed for the understanding of the progress and application of biocatalysis in stereodivergent synthesis.

Publication History

Received: 27 April 2022

Accepted: 12 July 2022

Article published online:
08 September 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

• References

• 1 Ali I, Gaitonde VD, Aboul-Enein HY, Hussain A. Chiral separation of β-adrenergic blockers on CelluCoat column by HPLC. Talanta 2009; 78 (02) 458-463
  CrossrefPubMedGoogle Scholar
• 2 He R, Fan J, Tan Q. et al. Enantioselective determination of metconazole in multi matrices by high-performance liquid chromatography. Talanta 2018; 178: 980-986
  CrossrefPubMedGoogle Scholar
• 3 Czerwenka C, Lämmerhofer M, Lindner W. Micro-HPLC and standard-size HPLC for the separation of peptide stereoisomers employing an ion-exchange principle. J Pharm Biomed Anal 2003; 30 (06) 1789-1800
  CrossrefPubMedGoogle Scholar
• 4 Harada N. HPLC separation of diastereomers: chiral molecular tools useful for the preparation of enantiopure compounds and simultaneous determination of their absolute configurations. Molecules 2016; 21 (10) 1328
  CrossrefPubMedGoogle Scholar
• 5 Beaufour M, Morin P, Ribet JP, Maurizot JC. HPLC quantitation of the four stereoisomers of benzoxathiepin derivatives with cellulose phenyl type chiral stationary phase and circular dichroism detection. J Pharm Biomed Anal 2006; 41 (02) 544-548
  CrossrefPubMedGoogle Scholar
• 6 Xiang DF, Bigley AN, Desormeaux E, Narindoshvili T, Raushel FM. Enzyme-catalyzed kinetic resolution of chiral precursors to antiviral prodrugs. Biochemistry 2019; 58 (29) 3204-3211
  CrossrefPubMedGoogle Scholar
• 7 Du J, Chu W, Zhang M, Ma C, Feng W. A novel method for preparing Eligulstat through chiral resolution. Bioorg Med Chem Lett 2020; 30 (16) 127209
  CrossrefPubMedGoogle Scholar
• 8 Turner NJ. Enzyme catalysed deracemisation and dynamic kinetic resolution reactions. Curr Opin Chem Biol 2004; 8 (02) 114-119
  CrossrefPubMedGoogle Scholar
• 9 Yamaguchi S, Mosher HS, Pohland A. Reversal in stereoselectivity depending upon the age of a chiral lithium alkoxyaluminohydride reducing agent. J Am Chem Soc 1972; 94 (26) 9254-9255
  CrossrefGoogle Scholar
• 10 Yamaguchi S, Mosher HS. Asymmetric reductions with chiral reagents from lithium aluminum hydride and (+)-(2S,3R)-4-dimethylamino-3-methyl-1, 2-diphenyl-2-butanol. J Org Chem 1973; 38 (10) 1870-1877
  CrossrefGoogle Scholar
• 11 Zanoni G, Castronovo F, Franzini M, Vidari G, Giannini E. Toggling enantioselective catalysis–a promising paradigm in the development of more efficient and versatile enantioselective synthetic methodologies. Chem Soc Rev 2003; 32 (03) 115-129
  CrossrefPubMedGoogle Scholar
• 12 Tanaka T, Hayashi M. New approach for complete reversal of enantioselectivity using a single chiral source. Synthesis 2008; 2008 (21) 3361-3376
  Article in Thieme ConnectGoogle Scholar
• 13 Ahrendt KA, Borths CJ, Macmillan DWC. New strategies for organic catalysis: the first highly enantioselective organocatalytic Diels—Alder reaction. J Am Chem Soc 2000; 31 (31) 4243-4244
  CrossrefGoogle Scholar
• 14 List B, Lerner RA, Barbas CF. Proline-catalyzed direct asymmetric aldol reactions. J Am Chem Soc 2000; 122 (10) 2395-2396
  CrossrefGoogle Scholar
• 15 Krautwald S, Carreira EM. Stereodivergence in asymmetric catalysis. J Am Chem Soc 2017; 139 (16) 5627-5639
  CrossrefPubMedGoogle Scholar
• 16 Gihani MT, Williams JM. Dynamic kinetic resolution. Curr Opin Chem Biol 1999; 3 (01) 11-15
  CrossrefPubMedGoogle Scholar
• 17 Gustafson JL, Lim D, Miller SJ. Dynamic kinetic resolution of biaryl atropisomers via peptide-catalyzed asymmetric bromination. Science 2010; 328 (5983): 1251-1255
  CrossrefPubMedGoogle Scholar
• 18 Wsól V, Skálová L, Szotáková B.. Chiral inversion of drugs: coincidence or principle?. Curr Drug Metab 2004; 5 (06) 517-533
  CrossrefPubMedGoogle Scholar
• 19 Ďuriš A, Wiesenganger T, Moravčíková D. et al. Expedient and practical synthesis of CERT-dependent ceramide trafficking inhibitor HPA-12 and its analogues. Org Lett 2011; 13 (07) 1642-1645
  CrossrefPubMedGoogle Scholar
• 20 Boesten WH, Seerden JP, de Lange B. et al. Asymmetric strecker synthesis of alpha-amino acids via a crystallization-induced asymmetric transformation using (R)-phenylglycine amide as chiral auxiliary. Org Lett 2001; 3 (08) 1121-1124
  CrossrefPubMedGoogle Scholar
• 21 Park H, Nandhakumar R, Hong J, Ham S, Chin J, Kim KM. Stereoconversion of amino acids and peptides in uryl-pendant binol schiff bases. Chemistry 2008; 14 (32) 9935-9942
  CrossrefPubMedGoogle Scholar
• 22 Lazzarotto M, Hammerer L, Hetmann M. et al. Chemoenzymatic total synthesis of deoxy-, epi-, and podophyllotoxin and a biocatalytic kinetic resolution of dibenzylbutyrolactones. Angew Chem Int Ed Engl 2019; 58 (24) 8226-8230
  CrossrefPubMedGoogle Scholar
• 23 Castro E, Soraci A, Fogel F, Tapia O. Chiral inversion of R(-) fenoprofen and ketoprofen enantiomers in cats. J Vet Pharmacol Ther 2000; 23 (05) 265-271
  CrossrefPubMedGoogle Scholar
• 24 Zhang R, Wang L, Xu Y. et al. In situ expression of (R)-carbonyl reductase rebalancing an asymmetric pathway improves stereoconversion efficiency of racemic mixture to (S)-phenyl-1,2-ethanediol in Candida parapsilosis CCTCC M203011. Microb Cell Fact 2016; 15 (01) 143
  CrossrefPubMedGoogle Scholar
• 25 Ogasawara Y, Dairi T. Peptide epimerization machineries found in microorganisms. Front Microbiol 2018; 9: 156
  CrossrefPubMedGoogle Scholar
• 26 Samuel J, Tanner ME. Mechanistic aspects of enzymatic carbohydrate epimerization. Nat Prod Rep 2002; 19 (03) 261-277
  CrossrefPubMedGoogle Scholar
• 27 Brenna E, Fuganti C, Gatti FG, Serra S. Biocatalytic methods for the synthesis of enantioenriched odor active compounds. Chem Rev 2011; 111 (07) 4036-4072
  CrossrefPubMedGoogle Scholar
• 28 Bicas JL, Dionísio AP, Pastore GM. Bio-oxidation of terpenes: an approach for the flavor industry. Chem Rev 2009; 109 (09) 4518-4531
  CrossrefPubMedGoogle Scholar
• 29 Guo J, Zhang R, Ouyang J. et al. Stereodivergent synthesis of carveol and dihydrocarveol through ketoreductases/ene‐reductases catalyzed asymmetric reduction. ChemCatChem 2018; 10 (23) 5496-5504
  CrossrefGoogle Scholar
• 30 Mori K. Absolute configuration of (−)-4-methylheptan-3-ol, a pheromone of the smaller european elm bark beetle, as determined by the synthesis of its (3R, 4R)-(+)-and (3S, 4R)-(+)-isomers. Tetrahedron 1977; 33 (03) 289-294
  CrossrefGoogle Scholar
• 31 Blight MM, Wadhams L, Wenham M. The stereoisomeric composition of the 4-methyl-3-heptanol produced by Scolytus scolytus and the preparation and biological activity of the four synthetic stereoisomers. Insect Biochem 1979; 9 (05) 525-533
  CrossrefGoogle Scholar
• 32 Ben-Yehuda S, Tolasch T, Francke W. et al. Aggregation pheromone of the almond bark beetle Scolytus amygdali (Coleoptera: Scolytidae). IOBC WPRS Bull 2002; 25: 1-12
  Google Scholar
• 33 Zada A, Ben-Yehuda S, Dunkelblum E, Harel M, Assael F, Mendel Z. Synthesis and biological activity of the four stereoisomers of 4-methyl-3-heptanol: main component of the aggregation pheromone of Scolytus amygdali. J Chem Ecol 2004; 30 (03) 631-641
  CrossrefPubMedGoogle Scholar
• 34 Attygalle AB, Vostrowsky O, Bestmann HJ, Steghaus-Kovac S, Maschwitz U. (3R,4S)-Methyl-3-heptanol, the trail pheromone of the ant Leptogenys diminuta . Naturwissenschaften 1988; 75 (06) 315-317
  CrossrefGoogle Scholar
• 35 Nakagawa N, Mori K. Pheromone synthesis. Part 68. Synthesis of (3S, 4S)-4-methyl-3-heptanol and its (3S, 4R)-isomer employing asymmetric epoxidation coupled with regioselective cleavage of epoxides with trimethylaluminum. Agric Biol Chem 1984; 48 (10) 2505-2510
  CrossrefGoogle Scholar
• 36 Unelius CR, Sandell J, Orrenius C. Enantioselective preparation of the stereoisomersof 4-methylheptan-3-ol using Candida antarctica lipase B. Collect Czech Chem Commun 1998; 63 (04) 525-533
  CrossrefGoogle Scholar
• 37 Brenna E, Crotti M, Gatti FG, Monti D, Parmeggiani F, Pugliese A. One-pot multi-enzymatic synthesis of the four stereoisomers of 4-methylheptan-3-ol. Molecules 2017; 22 (10) 1591
  CrossrefPubMedGoogle Scholar
• 38 Althoff EA, Wang L, Jiang L. et al. Robust design and optimization of retroaldol enzymes. Protein Sci 2012; 21 (05) 717-726
  CrossrefPubMedGoogle Scholar
• 39 Giger L, Caner S, Obexer R. et al. Evolution of a designed retro-aldolase leads to complete active site remodeling. Nat Chem Biol 2013; 9 (08) 494-498
  CrossrefPubMedGoogle Scholar
• 40 Garrabou X, Macdonald DS, Wicky BIM, Hilvert D. Stereodivergent evolution of artificial enzymes for the michael reaction. Angew Chem Int Ed Engl 2018; 57 (19) 5288-5291
  CrossrefPubMedGoogle Scholar
• 41 Miller SP, Zhong YL, Liu Z. et al. Practical and cost-effective manufacturing route for the synthesis of a β-lactamase inhibitor. Org Lett 2014; 16 (01) 174-177
  CrossrefPubMedGoogle Scholar
• 42 Balkovec JM, Hughes DL, Masurekar PS, Sable CA, Schwartz RE, Singh SB. Discovery and development of first in class antifungal caspofungin (CANCIDAS®)–a case study. Nat Prod Rep 2014; 31 (01) 15-34
  CrossrefPubMedGoogle Scholar
• 43 Harper S, McCauley JA, Rudd MT. et al. Discovery of MK-5172, a macrocyclic hepatitis C virus NS3/4a protease inhibitor. ACS Med Chem Lett 2012; 3 (04) 332-336
  CrossrefPubMedGoogle Scholar
• 44 Prier CK, Lo MMC, Li H, Yasuda N. Stereodivergent synthesis of 3‐hydroxyprolines and 3‐hydroxypipecolic acids via ketoreductase‐catalyzed dynamic kinetic reduction. Adv Synth Catal 2019; 361 (22) 5140-5143
  CrossrefGoogle Scholar
• 45 Zhu Y, Burgess K. Filling gaps in asymmetric hydrogenation methods for acyclic stereocontrol: application to chirons for polyketide-derived natural products. Acc Chem Res 2012; 45 (10) 1623-1636
  CrossrefPubMedGoogle Scholar
• 46 Schetter B, Mahrwald R. Modern aldol methods for the total synthesis of polyketides. Angew Chem Int Ed 2006; 45 (45) 7506-7525
  CrossrefPubMedGoogle Scholar
• 47 Hertweck C. The biosynthetic logic of polyketide diversity. Angew Chem Int Ed Engl 2009; 48 (26) 4688-4716
  CrossrefPubMedGoogle Scholar
• 48 Bailey CB, Pasman ME, Keatinge-Clay AT. Substrate structure-activity relationships guide rational engineering of modular polyketide synthase ketoreductases. Chem Commun (Camb) 2016; 52 (04) 792-795
  CrossrefPubMedGoogle Scholar
• 49 Robles ML. Ketoreductases as Biocatalysts in the Synthesis of Chiral Diketides [M.D. dissertation]. Austin, TE: Texas University; 2020
  Google Scholar
• 50 Degnan AP, Huang H, Snyder LB, Yang F, Gillman KW, Parker MF. Oxazolidinones as modulators of mGluR5. U.S. Patent 8691821. April, 2014
  PubMedGoogle Scholar
• 51 Yang F, Snyder LB, Balakrishnan A. et al. Discovery and preclinical evaluation of BMS-955829, a potent positive allosteric modulator of mGluR5. ACS Med Chem Lett 2016; 7 (03) 289-293
  CrossrefPubMedGoogle Scholar
• 52 Hanson RL, Guo Z, González-Bobes F, Fenster MD, Goswami A. Enzymatic reduction of α-substituted ketones with concomitant dynamic kinetic resolution. J Mol Catal, B Enzym 2016; 133: 20-26
  CrossrefGoogle Scholar
• 53 Huerta FF, Minidis ABE, Bäckvall JE. Racemisation in asymmetric synthesis. Dynamic kinetic resolution and related processes in enzyme and metal catalysis. Chem Soc Rev 2001; 30 (06) 321-331
  CrossrefGoogle Scholar
• 54 DeHovitz JS, Loh YY, Kautzky JA. et al. Static to inducibly dynamic stereocontrol: the convergent use of racemic β-substituted ketones. Science 2020; 369 (6507): 1113-1118
  CrossrefPubMedGoogle Scholar
• 55 Kleemann A, Engels J, Kutscher B, Reichert D. Pharmaceutical Substances: Syntheses, Patents, Applications. 5th ed. Stuttgart: Thieme; 2008
  Google Scholar
• 56 Bode SE, Wolberg M, Mueller M. Stereoselective synthesis of 1,3-diols. Synthesis 2006; 2006 (04) 557-588
  Article in Thieme ConnectGoogle Scholar
• 57 Binder JT, Kirsch SF. Iterative approach to polyketide-type structures: stereoselective synthesis of 1,3-polyols utilizing the catalytic asymmetric Overman esterification. Chem Commun (Camb) 2007; (40) 4164-4166
  CrossrefPubMedGoogle Scholar
• 58 Börner A. Phosphorous Ligands in Asymmetric Catalysis—Synthesis and Applications. 1st ed. Weinheim: Wiley-VCH; 2008
  Google Scholar
• 59 Baer K, Krausser M, Burda E, Hummel W, Berkessel A, Gröger H. Sequential and modular synthesis of chiral 1,3-diols with two stereogenic centers: access to all four stereoisomers by combination of organo- and biocatalysis. Angew Chem Int Ed Engl 2009; 48 (49) 9355-9358
  CrossrefPubMedGoogle Scholar
• 60 Sonoike S, Itakura T, Kitamura M, Aoki S. One-pot chemoenzymatic synthesis of chiral 1,3-diols using an enantioselective aldol reaction with chiral Zn2+ complex catalysts and enzymatic reduction using oxidoreductases with cofactor regeneration. Chem Asian J 2012; 7 (01) 64-74
  CrossrefPubMedGoogle Scholar
• 61 Ma S. Electrophilic addition and cyclization reactions of allenes. Acc Chem Res 2009; 42 (10) 1679-1688
  CrossrefPubMedGoogle Scholar
• 62 Gilmore K, Alabugin IV. Cyclizations of alkynes: revisiting Baldwin's rules for ring closure. Chem Rev 2011; 111 (11) 6513-6556
  CrossrefPubMedGoogle Scholar
• 63 Saha P, Saikia AK. Ene cyclization reaction in heterocycle synthesis. Org Biomol Chem 2018; 16 (16) 2820-2840
  CrossrefPubMedGoogle Scholar
• 64 Tannert R, Milroy LG, Ellinger B, Hu TS, Arndt HD, Waldmann H. Synthesis and structure-activity correlation of natural-product inspired cyclodepsipeptides stabilizing F-actin. J Am Chem Soc 2010; 132 (09) 3063-3077
  CrossrefPubMedGoogle Scholar
• 65 Tannert R, Hu TS, Arndt HD, Waldmann H. Solid-phase based total synthesis of Jasplakinolide by ring-closing metathesis. Chem Commun (Camb) 2009; (12) 1493-1495
  CrossrefPubMedGoogle Scholar
• 66 Fürstner A, Bouchez LC, Morency L. et al. Total syntheses of amphidinolides B1, B4, G1, H1 and structure revision of amphidinolide H2. Chemistry 2009; 15 (16) 3983-4010
  CrossrefPubMedGoogle Scholar
• 67 Classen T, Korpak M, Schölzel M, Pietruszka J. Stereoselective enzyme cascades: an efficient synthesis of chiral γ-butyrolactones. ACS Catal 2014; 4 (05) 1321-1331
  CrossrefGoogle Scholar
• 68 Simon RC, Busto E, Schrittwieser JH. et al. Stereoselective synthesis of γ-hydroxynorvaline through combination of organo- and biocatalysis. Chem Commun (Camb) 2014; 50 (99) 15669-15672
  CrossrefPubMedGoogle Scholar
• 69 Besse P, Veschambre H. Chemoenzymatic synthesis of “α-bichiral” synthons. Application to the preparation of chiral epoxides. Tetrahedron Asymmetry 1993; 4 (06) 1271-1285
  CrossrefGoogle Scholar
• 70 Coelho PS, Brustad EM, Kannan A, Arnold FH. Olefin cyclopropanation via carbene transfer catalyzed by engineered cytochrome P450 enzymes. Science 2013; 339 (6117): 307-310
  CrossrefPubMedGoogle Scholar
• 71 Gober JG, Rydeen AE, Gibson-O'Grady EJ, Leuthaeuser JB, Fetrow JS, Brustad EM. Mutating a highly conserved residue in diverse cytochrome P450s facilitates diastereoselective olefin cyclopropanation. ChemBioChem 2016; 17 (05) 394-397
  CrossrefPubMedGoogle Scholar
• 72 Knight AM, Kan SBJ, Lewis RD, Brandenberg OF, Chen K, Arnold FH. Diverse engineered heme proteins enable stereodivergent cyclopropanation of unactivated alkenes. ACS Cent Sci 2018; 4 (03) 372-377
  CrossrefPubMedGoogle Scholar
• 73 Zhang Z, Cepeda AJ, Robles ML. et al. General chemoenzymatic route to two-stereocenter triketides employing assembly line ketoreductases. Chem Commun (Camb) 2019; 56 (01) 157-160
  CrossrefPubMedGoogle Scholar
• 74 Breuer M, Ditrich K, Habicher T. et al. Industrial methods for the production of optically active intermediates. Angew Chem Int Ed 2004; 43 (07) 788-824
  CrossrefPubMedGoogle Scholar
• 75 Sehl T, Maugeri Z, Rother D. Multi-step synthesis strategies towards 1, 2-amino alcohols with special emphasis on phenylpropanolamines. J Mol Catal, B Enzym 2015; 114: 65-71
  CrossrefGoogle Scholar
• 76 Gupta P, Mahajan N. Biocatalytic approaches towards the stereoselective synthesis of vicinal amino alcohols. New J Chem 2018; 42 (15) 12296-12327
  CrossrefGoogle Scholar
• 77 Corrado ML, Knaus T, Mutti FG. Regio- and stereoselective multi-enzymatic aminohydroxylation of β-methylstyrene using dioxygen, ammonia and formate. Green Chem 2019; 21 (23) 6246-6251
  CrossrefPubMedGoogle Scholar
• 78 Corrado ML, Knaus T, Mutti FG. High regio‐and stereoselective multi‐enzymatic synthesis of all phenylpropanolamine stereoisomers from β‐methylstyrene. ChemBioChem 2021; 22 (13) 2345-2350
  CrossrefPubMedGoogle Scholar
• 79 Serebryakov EP. Stereodivergent synthesis of chiral low-molecular bioregulators using readily available lipases. Russ Chem Bull 2001; 50 (11) 1984-1997
  CrossrefGoogle Scholar
• 80 Wikmark Y, Svedendahl Humble M, Bäckvall JE. Combinatorial library based engineering of Candida antarctica lipase A for enantioselective transacylation of sec-alcohols in organic solvent. Angew Chem Int Ed Engl 2015; 54 (14) 4284-4288
  CrossrefPubMedGoogle Scholar
• 81 Xu J, Cen Y, Singh W. et al. Stereodivergent protein engineering of a lipase to access all possible stereoisomers of chiral esters with two stereocenters. J Am Chem Soc 2019; 141 (19) 7934-7945
  CrossrefPubMedGoogle Scholar
• 82 Huang PS, Boyken SE, Baker D. The coming of age of de novo protein design. Nature 2016; 537 (7620): 320-327
  CrossrefPubMedGoogle Scholar
• 83 Spence MA, Kaczmarski JA, Saunders JW, Jackson CJ. Ancestral sequence reconstruction for protein engineers. Curr Opin Struct Biol 2021; 69: 131-141
  CrossrefPubMedGoogle Scholar
• 84 Harrison W, Huang X, Zhao H. Photobiocatalysis for abiological transformations. Acc Chem Res 2022; 55 (08) 1087-1096
  CrossrefPubMedGoogle Scholar
• 85 Wan L, Heath RS, Megarity CF. et al. Exploiting bidirectional electrocatalysis by a nanoconfined enzyme cascade to drive and control enantioselective reactions. ACS Catal 2021; 11 (11) 6526-6533
  CrossrefGoogle Scholar
• 86 Guo K, Qian K, Zhang S, Kong J, Yu C, Liu B. Bio-electrocatalysis of NADH and ethanol based on graphene sheets modified electrodes. Talanta 2011; 85 (02) 1174-1179
  CrossrefPubMedGoogle Scholar