Abstract
Several recently accomplished total syntheses of antibiotic natural products were summarized in this review in order to present current trends in this area of research. Compounds from different substance classes, including polyketide, depsipeptide, polyketide–polypeptide hybrid, and saccharide, were chosen to demonstrate the advancement in both chemical methodology and corresponding synthetic strategy.
Similar content being viewed by others
References
Abiko A, Moriya O, Filla SA, Masamune S (1995) Benzopyranoisoxazolidines as chiral auxiliaries for asymmetric synthesis. Angew Chem Int Ed 34:793–795, Angew Chem 107:869–871
Andrews MD, Brewster AG, Crapnell KM, Ibbett AJ, Jones T, Moloney MG, Prout K, Watkin D (1998) Regioselective Dieckmann cyclisations leading to enantiopure highly functionalised tetramic acid derivatives. J Chem Soc Perkin Trans 1: Organic and Bio-Organic Chemistry 223–236
Appel R (1975) Tertiary phosphane/tetrachloromethane, a versatile reagent for chlorination, dehydration, and P-N linkage. Angew Chem Int Ed 14:801–811, Angew Chem 87:863–874
Arai M, Haneishi T, Kitahara N, Enokita R, Kawakubo K, Kondo Y (1976) Herbicidins A and B, two new antibiotics with herbicidal activity. I. Producing organism and biological activities. J Antibiot 29:863–869
Artsimovitch I, Vassylyeva MN, Svetlov D, Svetlov V, Perederina A, Igarashi N, Matsugaki N, Wakatsuki S, Tahirov TH, Vassylyev DG (2005) Allosteric modulation of the RNA polymerase catalytic reaction is an essential component of transcription control by rifamycins. Cell 122:351–363
Augustiniak H, Höfle G, Irschik H, Reichenbach H (1996) Antibiotics from gliding bacteria, LXXVIII. Ripostatin A, B, and C: Isolation and structure elucidation of novel metabolites from Sorangium cellulosum. Liebigs Ann 1657–1663
Bal BS, Childers WE, Pinnick HW (1981) Oxidation of α, β-unsaturated aldehydes. Tetrahedron 37:2091–2096
Barrière JC, Paris JM (1993) RP 59500 and related semisynthetic streptogramins. Drugs Future 18:833–845
Barrière JC, Bouanchaud D, Desnoottes JF, Paris JM (1994) Streptogramin analogues. Expert Opin Investig Drugs 3:115–131
Blakemore PR, Cole WJ, Kocieński PJ, Morley A (1998) A stereoselective synthesis of trans-1,2-disubstituted alkenes based on the condensation of aldehydes with metallated 1-Phenyl-1H-tetrazol-5-yl sulfones. Synlett 26–28
L. Boulard, S. BouzBouz, J. M. Paris, J. Cossy, Synthesis of the C1-C13 Fragment of (+)-Callipeltoside A Synlett (2007) 1461 – 1463. [84] b)
Bouzide A, Sauve G (1997) Highly selective silver(I) oxide mediated monoprotection of symmetrical diols. Tetrahedron Lett 38:5945–5948
Brill GM, McAlpine JB, Whittern DJ (1988) Tirandalydigin, a novel tetramic acid of the tirandamycin-streptolydigin type. I. Taxonomy of the producing organism, fermentation and biological activity. Antibiot 41:36–44
Brochu MP, Brown SP, MacMillan DWC (2004) Direct and enantioselective organocatalytic α-chlorination of aldehydes. J Am Chem Soc 126:4108–4109
Brown HC, Jadhav PK (1983) Asymmetric carbon-carbon bond formation via β-allyldiisopinocampheylborane. Simple synthesis of secondary homoallylic alcohols with excellent enantiomeric purities. J Am Chem Soc 105:2092–2093
Campbell EA, Korzheva N, Mustaev A, Murakami K, Nair S, Goldfarb A, Darst SA (2001) Structural mechanism for rifampicin inhibition of bacterial RNA Polymerase. Cell 104:901–912
Carlson JC, Li S, Burr DA, Sherman DH (2009) Isolation and characterization of tirandamycins from a marine-derived Streptomyces sp. J Nat Prod 72:2076–2079
Chaturvedi D (2012) Perspectives on the synthesis of organic carbamates. Tetrahedron 68:15–45
Chen YK, Walsh PJ (2004) A one-pot multicomponent coupling reaction for the stereocontrolled synthesis of (Z)-trisubstituted allylic alcohols. J Am Chem Soc 126:3702–3703
Cipolla L, Lay L, Nicotra F (1997) New and easy access to C-glycosides of glucosamine and mannosamine. J Org Chem 62:6678–6681
Corey EJ, Helal CJ (1998) Reduction of carbonyl compounds with chiral oxazaborolidine catalysts: a new paradigm for enantioselective catalysis and a powerful new synthetic method. Angew Chem Int Ed 37:1986–2012, Angew Chem 110:2092–2118
Corey EJ, Nicolaou KC (1974) Efficient and mild lactonization method for the synthesis of macrolides. J Am Chem Soc 96:5614–5616
Cowden CJ, Paterson I (1997) Asymmetric aldol reactions using boron enolates. Org React 51:1–200
DeBoer C, Dietz A, Silver WS, Savage GM (1956) Streptolydigin, a new antimicrobial antibiotic. I. Biologic studies of streptolydigin. Antibiot Annu 886–892
Delpierre GR, Eastwood FW, Gream GE, Kingston DGI, Todd ARL, Williams DH (1966) Antibiotics of the ostreogrycin complex. Part II. Structure of ostreogrycin A J Chem So. C 1653–1669
DeMico A, Margarita R, Parlanti L, Vescovi A, Piancatelli GA (1997) Versatile and highly selective hypervalent iodine (III)/2,2,6,6-tetramethyl-1-piperidinyloxyl-mediated oxidation of alcohols to carbonyl compounds. J Org Chem 62:6974–6977
Dess DB, Martin JC (1983) Readily accessible 12-I-5 oxidant for the conversion of primary and secondary alcohols to aldehydes and ketones. J Org Chem 48:4155–4156
Dhar RK (1994) Diisopinocamphenylchloroborane, (DIP-Chloride), an excellent chiral reducing reagent for the synthesis of secondary alcohols of high enantiomeric purity. Aldrichim Acta 27:43–51
Eble TE, Large CM, DeVries WH, Crum GF, Shell JW (1956) Streptolydigin, a new antimicrobial antibiotic. II. Isolation and characterization. Antibiot Annu 893–896
Edmonds DJ, Johnston D, Procter DJ (2004) Samarium(II)-iodide-mediated cyclizations in natural product synthesis. Chem Rev 104:3371–3404
Erol Ö, Schäberle TF, Schmitz A, Rachid S, Gurgui C, El-Omari M, Lohr F, Kehraus S, Piel J, Müller R, König GM (2010) Biosynthesis of the myxobacterial antibiotic corallopyronin A. ChemBioChem 11:1253–1265
Eto K, Yoshino M, Takahashi K, Ishihara J, Hatakeyama S (2011) Total synthesis of oxazolomycin A. Org Lett 13:5398–5401
Evans DA, Britton TC (1987) Electrophilic azide transfer to chiral enolates. A general approach to the asymmetric synthesis of α-amino acids. J Am Chem Soc 109:6881–6883
Evans DA, Hoveyda AH (1990) Samarium-catalyzed intramolecular Tishchenko reduction of β-hydroxy ketones. A stereoselective approach to the synthesis of differentiated anti-1,3-diol monoesters. J Am Chem Soc 112:6447–6449
Evans DA, Chapman KT, Carreira EM (1988) Directed reduction of α-hydroxy ketones employing tetramethylammonium triacetoxyborohydride. J Am Chem Soc 110:3560–3578
Farina V, Krishnamurthy V (1998) Scott WJ in “The Stille reaction”. Org React 50:1–652
Felzmann W, Castagnolo D, Rosenbeiger D, Mulzer J (2007) Crotylation versus propargylation: two routes for the synthesis of the C13–C18 fragment of the antibiotic branimycin. J Org Chem 72:2182–2186
Fischer M-R, Kirschning A, Michel T, Schaumann E (1994) Syntheses of cyclopentanols by a silicon-induced cascade reaction. Angew Chem Int Ed 33:217–218, Angew Chem 106:220-221
Frantz DE, Fassler R, Carreira EM (2000) Facile enantioselective synthesis of propargylic alcohols by direct addition of terminal alkynes to aldehydes. J Am Chem Soc 122:1806–1807
Freeman PK, Hutchinson LL (1980) Alkyllithium reagents from alkyl halides and lithium radical anions. J Org Chem 45:1924–1930
Ganesan A (2008) The impact of natural products upon modern drug discovery. Curr Opin Chem Biol 12:306–317
Glaus F, Altmann KH (2012) Total synthesis of the bacterial RNA polymerase inhibitor ripostatin B. Angew Chem Int Ed 51:3405–3409, Angew Chem 124:3461–3465
Gräfe U, Kluge H, Thiericke R (1992) Biogenetic studies on oxazolomycin, a metabolite of Streptomyces albus (strain JA 3453). Liebigs Ann Chem 429–432
Gromov A, Enev VS, Mulzer J (2009) A desymmetrization approach toward highly oxygenated cis-decalins. Org Lett 11:2884–2886
Guthrie AE, Semple JE, Joullié MM (1982) Synthetic studies of fungal metabolites: ascofuranone and colletochlorin D. J Org Chem 47:2369–2376
Hagenmaier H, Jaschke KH, Santo L, Scheer M, Zahner H (1976) Metabiolic products of microorganisms. Tirandamycin B. (in German). Arch Microbiol 109:65–74
Hager D, Mayer P, Paulitz C, Tiebes J, Trauner D (2012) Stereoselective total syntheses of herbicidin C and aureonuclemycin through late-stage glycosylation. Angew Chem Int Ed 51:6525–6528, Angew Chem 124:6631–6634
Halland N, Braunton A, Bachmann S, Marigo M, Jørgensen KA (2004) Direct organocatalytic asymmetric α-chlorination of aldehydes. J Am Chem Soc 126:4790–4791
Hamann MT (2003) Enhancing marine natural product structural diversity and bioactivity through semisynthesis and biocatalysis. Curr Pharm Des 9:879–889
Haneishi T, Terahara A, Kayamori H, Yabe J, Arai M (1976) Herbicidins A and B, two new antibiotics with herbicidal activity II. Fermentation, isolation and physico-chemical characterization. J Antibiot 29:870–875
Hermitage SA, Cardwell KS, Chapman T, Cooke JWB, Newton R (2001) An efficient, practical approach to the synthesis of 2,4-disubstituted thiazoles and oxazoles: application to the synthesis of GW475151. Org Process Res Dev 5:37–44
Hu T, Schaus JV, Lam K, Palfreyman MG, Wuonola M, Gustafson G, Panek JS (1998) Total synthesis and preliminary antibacterial evaluation of the RNA polymerase inhibitors (±)-myxopyronin A and B. J Org Chem 63:2401–2406
Hughes DL (1992) The Mitsunobu Reaction. Org React 42:335–656
Inanaga J, Hirata K, Saeki H, Katsuki T, Yamaguchi M (1979) A rapid esterification by means of mixed anhydride and its application to large-ring lactonization. Bull Chem Soc Jpn 52:1989–1993
Irschik H, Gerth K, Höfle G, Kohl W, Reichenbach H (1983) The myxopyronins, new inhibitors of bacterial RNA synthesis from Myxococcus fulvus (Myxobacterales). J Antibiot 36:1651–1658
Irschik H, Jansen R, Höfle G, Gerth K, Reichenbach H (1985) The corallopyronins, new inhibitors of bacterial RNA synthesis from Myxobacteria. J Antibiot 38:145–152
Irschik H, Augustiniak H, Gerth K, Höfle G, Reichenbach H (1995) The ripostatins, novel inhibitors of eubacterial RNA polymerase isolated from myxobacteria. J Antibiot 48:787–792
Irschik H, Schummer D, Höfle G, Reichenbach H, Steinmetz H, Jansen R (2007) Etnangien, a macrolide-polyene antibiotic from Sorangium cellulosum that inhibits nucleic acid polymerases. J Nat Prod 70:1060–1063
Jansen R, Irschik H, Reichenbach H, Höfle G (1985) Corallopyronin A, B, and C: three novel antibiotics from Corallocuccus coralloides Cc c127 (Myxobacterales). (in German) Liebigs Ann Chem 822–836
Jesse WHL, Vederas JC (2009) Drug discovery and natural products: end of an era or an endless frontier? Science 325:161–165
Johnson WS, Gravestock MB, McCarry BE (1970) Simple stereoselective version of the Claisen rearrangement leading to trans-trisubstituted olefinic bonds. Synthesis of squalene. J Am Chem Soc 92:741–743
Kanematsu M, Shindo M, Yoshida M, Shishido K (2009) Total synthesis of bongkrekic acid via sequential Suzuki-Miyaura coupling reactions. Synthesis 2893–2904
Kawai S, Kawabata G, Kobayashi A, Kawazu K (1989) Inhibitory effect of oxazolomycin on crown gall formation. Agric Biol Chem 53:1127–1133
Kende AS, Kawamura K, DeVita RJ (1990) Enantioselective total synthesis of neooxazolomycin. J Am Chem Soc 112:4070–4072
Kirschning A, Hahn F (2012) Merging chemical synthesis and biosynthesis: a new chapter in the total synthesis of natural products and natural product libraries. Angew Chem Int Ed 51:4012–4022
Kujat C, Bock M, Kirschning A (2006) Synthesis of the the C1-C5 and C6-C24 Fragments of the RNA-polymerase inhibitors Ripostatin A and B. Synlett 419–422
Lewis C, Wilkins JR, Schwartz DF, Nikitas CT (1956) Streptolydigin, a new antimicrobial antibiotic. III. In vitro and in vivo laboratory studies. Antibiot Annu 897–902
Lewis MD, Cha JK, Kishi Y (1982) Highly stereoselective approaches to α-and β-C-glycopyranosides. J Am Chem Soc 104:4976–4978
Ley SV, Madin A, In Comprehensive organic synthesis, Trost BM (Ed.), I. Fleming (Ed.) vol. 7 pp 253–256 (1991) ISBN ISBN: 978-0-08-052349-1
Ley SV, Smith SC, Woodward PR (1992) Further reactions of t-butyl 3-oxobutanthioate and t-butyl 4-diethyl-phosphono-3-oxobutanthioate: carbonyl coupling reactions, amination, use in the preparation of 3-acyltetramic acids and application to the total synthesis of fuligorubin A. Tetrahedron 48:1145–1174
Li P, Li J, Arikan F, Ahlbrecht W, Dieckmann M, Menche D (2009) Total synthesis of etnangien. J Am Chem Soc 131:11678–11679
Lira R, Agrios KA, Doundoulakis T, Simonsen KB, Webber SE, Xiang AX (2006) An efficient synthesis of (±)-myxopyronin B via versatile pyridone intermediates. Heterocycles 68:1099–1103
Lokot IP, Pashkovsky FS, Lakhvieh FA (1999) A new approach to the synthesis of 3,6- and 5,6-dialkyl derivatives of 4-hydroxy-2-pyrone. Synthesis of rac-germicidin. Tetrahedron 55:4783–4792
Maier ME (2009) Structural revisions of natural products by total synthesis. Nat Prod Rep 26:1105–1124
Marchart S, Gromov A, Mulzer J (2010) Total synthesis of the antibiotic branimycin. Angew Chem Int Ed 49:2050–2053, Angew Chem 122:2094–2097
Menche D, Arikan F, Perlova O, Horstmann N, Ahlbrecht W, Wenzel SC, Jansen R, Irschik H, Müller R (2008) Stereochemical determination and complex biosynthetic assembly of etnangien, a highly potent RNA polymerase inhibitor from the myxobacterium Sorangium cellulosum. J Am Chem Soc 130:14234–14243
Meyer CEJ (1971) Tirandamycin, a new antibiotic isolation and characterization. Antibiot 24:558–560
Moloney MG, Trippier PC, Yaqoob M, Wang Z (2004) The oxazolomycins: a structurally novel class of bioactive compounds. Curr Drug Discov Tech 1:181–199
Mori T, Takakashi K, Kashiwabara M, Uemura D, Katayama C, Iwadare S, Shizuri Y, Mitomo R, Nakano F, Matsuzaki A (1985) Structure of oxazolomycin, a novel β-lactone antibiotic. Tetrahedron Lett 26:1073–1076
Moser WH (2001) The Brook rearrangement in tandem bond formation strategies. Tetrahedron 57:2065–2084
Mukhopadhyay J, Das K, Ismail S, Koppstein D, Jang M, Hudson B, Sarafianos S, Tuske S, Patel J, Jansen R, Irschik H, Arnold E, Ebright RH (2008) The RNA polymerase “switch region” is a target for inhibitors. Cell 135:295–307
Neises B, Steglich W (1978) Simple method for the esterification of carboxylic acids. Angew Chem Int Ed 17:522–524, Angew Chem 90:556–557
Nicolaou KC, Snyder SA (2005) Chasing molecules that were never there: misassigned natural products and the role of chemical synthesis in modern structure elucidation. Angew Chem Int Ed 44:1012–1044, Angew Chem 117:1036–1069
Nicolaou KC, Harter MW, Gunzner JL, Nadin A (1997) The Wittig and related reactions in natural product synthesis. Liebigs Ann/Rec 1283–1301
Onyango EO, Tsurumoto J, Imai N, Takahashi K, Ishihara J, Hatakeyama S (2007) Total synthesis of neooxazolomycin. Angew Chem Int Ed 46:6703–6705, Angew Chem 119:6823–6825
Paterson I, Tillyer RD (1992) Studies in polypropionate synthesis: high π-face selectivity in syn aldol reactions of tin(II) enolates from (R)- and (S)-1-benzyloxy-2-methylpentan-3-one. Tetrahedron Lett 33:4233–4236
Pronin SV, Kozmin SA (2010) Synthesis of streptolydigin, a potent bacterial RNA polymerase inhibitor. J Am Chem Soc 132:14394–14396
Pronin SV, Martinez A, Kuznedelov K, Severinov K, Shuman HA, Kozmin SA (2011) Chemical synthesis enables biochemical and antibacterial evaluation of streptolydigin antibiotics. J Am Chem Soc 133:12172–12184
Reichard HA, Rieger JC, Micalizio GC (2008) Total synthesis of callystatin-A by titanium-mediated reductive alkyne–alkyne cross-coupling. Angew Chem Int Ed 47:7837–7840, Angew Chem 120:7955–7958
Rentsch A, Kalesse M (2012) The total synthesis of corallopyronin A and myxopyronin B. Angew Chem Int Ed 51:11381–11384, Angew Chem 124:11543–11547
Sato M, Sakakl J, Sugita Y, Yasuda S, Sakoda H, Kaneko C (1991) Two lactone formation reactions from 1,3-dioxin-4-ones having hydroxyalkyl group at the 6-position: Difference in ring opening and closure. Tetrahedron 47:5689–5708
Schaus SE, Brandes BD, Larrow JF, Tokunaga M, Hansen KB, Gould AE, Furrow ME, Jacobsen EN (2002) Highly selective hydrolytic kinetic resolution of terminal epoxides catalyzed by chiral (salen)CoIII complexes. Practical synthesis of enantioenriched terminal epoxides and 1,2-diols. J Am Chem Soc 124:1307–1315
Schlessinger RH, Graves DD (1987) A non-congener based synthesis of L-(-)-rhodinose and of a C4 hydroxyl protected derivative. Tetrahedron Lett 28:4381–4384
Schlessinger RH, Li Y-J (1996) Total synthesis of (–)-Virginiamycin M2 using 2nd-generation vinylogous urethane chemistry. J Am Chem Soc 118:3301–3302
Shimshock SJ, Waltermire RE, DeShong P (1991) A total synthesis of (+)-tirandamycin B. J Am Chem Soc 113:8791–8796
Speitling M, Grün-Wollny I, Hannske FG, Laatsch H (2000 and 2001) Poster presentations at 12 and 13 IRSEER Naturstofftage der DECHEMA e.V. Irsee
Takahashi K, Kawabata M, Uemura D, Iwadare S, Mitomo R, Nakano F, Matsuzaki A (1985) Structure of neooxazolomycin, an antitumor antibiotic. Tetrahedron Lett 26:1077–1078
Takahashi K, Midori M, Kawano K, Ishihara J, Hatakeyama S (2008) Entry to heterocycles based on indium-catalyzed Conia-ene reactions: asymmetric synthesis of (−)-salinosporamide A. Angew Chem Int Ed 47:6244–6246, Angew Chem 120:6340–6342
Takai K, Nozaki H (2000) Nucleophilic addition of organochromium reagents to carbonyl compounds. Proc Jpn Acad Ser B 76:123–131
Takai K, Nitta K, Utimoto K (1986) Simple and selective method for aldehydes (RCHO) → (E)-haloalkenes (RCH=CHX) conversion by means of a haloform-chromous chloride system. J Am Chem Soc 108:7408–7410
Tang W, Prusov EV (2012a) Total synthesis of ripostatin A. Org Lett 14:4690–4693
Tang WF, Prusov EV (2012b) Total synthesis of RNA-polymerase inhibitor ripostatin B and 15-deoxyripostatin A. Angew Chem Int Ed 51:3401–3404, Angew Chem 124:3457–3460
Trost BM, Gunzner JL (2001) Total synthesis of deschlorocallipeltoside A. J Am Chem Soc 123:9449–9450
Trost BM, Papillon JPN (2004) Alkene−alkyne coupling as a linchpin: an efficient and convergent synthesis of amphidinolide P. J Am Chem Soc 126:13618–13619
Tuske S, Sarafianos SG, Wang X, Hudson B, Sineva E, Mukhopadhyay J, Birktoft JJ, Leroy O, Ismail S, Clark AD, Dharia C, Napoli A, Laptenko O, Lee J, Borukhov S, Ebright RH, Arnold E (2005) Inhibition of bacterial RNA polymerase by streptolydigin: stabilization of a straight-bridge-helix active-center conformation. Cell 122:541–552
VanRheenen V, Kelly RC, Cha DY (1976) An improved catalytic OsO4 oxidation of olefins to cis-1,2-glycols using tertiary amine oxides as the oxidant. Tetrahedron Lett 17:1973–1976
Vorbrüggen H, Bennua B (1981) Nucleoside syntheses, XXV. A new simplified nucleoside synthesis. Chem Ber 114:1279–1286
Williams JM, Jobson RB, Yasuda N, Marchesini G, Dolling UH, Grabowski EJJ (1995) A new general method for preparation of N-methoxy-N-methylamides. Application in direct conversion of an ester to a ketone. Tetrahedron Lett 36:5461–5464
Winter P, Swatschek J, Willot M, Radtke L, Olbrisch T, Schäfer A, Christmann M (2011) Transforming terpene-derived aldehydes into 1,2-epoxides via asymmetric α-chlorination: subsequent epoxide opening with carbon nucleophiles. Chem Commun 47:12200–12202
Winter P, Hiller W, Christmann M (2012) Access to skipped polyene macrolides through ring-closing metathesis: total synthesis of the RNA polymerase inhibitor ripostatin B. Angew Chem Int Ed 51:3396–3400, Angew Chem 124:3452–3456
Wu J, Panek JS (2010) Total synthesis of (–)-Virginiamycin M2. Angew Chem Int Ed 49:6165–6168, Angew Chem 122:6301–6304
Wu J, Chen Y, Panek JS (2010) Vinylogous aldol products from chiral crotylsilanes obtained by enantioselective Rh(II) and Cu(I) carbenoid Si−H insertion. Org Lett 12:2112–2115
Zhu C, Shen X, Nelson SG (2004) Cinchona alkaloid-Lewis acid catalyst systems for enantioselective ketene−aldehyde cycloadditions. J Am Chem Soc 126:5352–5353
Zottola MA, Alonso R, Vite GD, Fraserreid B (1989) A practical, efficient large-scale synthesis of 1,6-anhydrohexopyranoses. J Org Chem 54:6123–6125
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
ESM 1
(PDF 162 kb)
Rights and permissions
About this article
Cite this article
Prusov, E.V. Total synthesis of antibiotics: recent achievements, limitations, and perspectives. Appl Microbiol Biotechnol 97, 2773–2795 (2013). https://doi.org/10.1007/s00253-013-4757-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00253-013-4757-5