Synthesis of Lincosamide Analogues via Oxime Resin Aminolysis

Thomas Tremblay; Pénélope Haguette; Gabrielle Robert-Scott; Jessica B. Alcée; Christopher Bérubé; Catherine Bergeron; Normand Voyer; Denis Giguère

doi:10.1055/a-1948-7153

Synlett, Table of Contents

Synlett 2023; 34(01): 40-44
DOI: 10.1055/a-1948-7153

letter

Synthesis of Lincosamide Analogues via Oxime Resin Aminolysis

Thomas Tremblay

^aDépartement de Chimie, 1045 Avenue de la Médecine, Université Laval, Québec City, Québec, G1V 0A6, Canada

,

Pénélope Haguette

^aDépartement de Chimie, 1045 Avenue de la Médecine, Université Laval, Québec City, Québec, G1V 0A6, Canada

,

Gabrielle Robert-Scott

^aDépartement de Chimie, 1045 Avenue de la Médecine, Université Laval, Québec City, Québec, G1V 0A6, Canada

,

Jessica B. Alcée

^aDépartement de Chimie, 1045 Avenue de la Médecine, Université Laval, Québec City, Québec, G1V 0A6, Canada

,

Christopher Bérubé

^aDépartement de Chimie, 1045 Avenue de la Médecine, Université Laval, Québec City, Québec, G1V 0A6, Canada

,

Catherine Bergeron

^aDépartement de Chimie, 1045 Avenue de la Médecine, Université Laval, Québec City, Québec, G1V 0A6, Canada

,

Normand Voyer

^aDépartement de Chimie, 1045 Avenue de la Médecine, Université Laval, Québec City, Québec, G1V 0A6, Canada

,

Denis Giguère ∗

^aDépartement de Chimie, 1045 Avenue de la Médecine, Université Laval, Québec City, Québec, G1V 0A6, Canada

› Author Affiliations

Abstract

All articles of this category

Abstract

In this work, the synthetic development of an oxime resin aminolysis to lincosamide analogues is described. This synthetic endeavor hinges on a protecting-group-free strategy of the amino sugar nucleophiles. The cleavage from the solid support is achieved under mild conditions in a buffer solution and allows the preparation of a wide diversity of amino acid moieties onto glycosylamine scaffolds. The strategy is further exploited using methylthiolincosamine to generate rapidly complex lincomycin analogues. The results pave the way to access efficiently novel potentially relevant antibacterial compounds.

Key words

lincosamide analogues - oxime resin aminolysis - protecting-group-free synthesis - lincomycin analogues - antibacterial compounds - solid-phase synthesis

Full Text

References

References and Notes
1 Spizek J, Novotna J, Rezanka T. Adv. Appl. Microbiol. 2004; 56: 121

2a Schlunzen F, Zarivach R, Harms J, Bashan A, Tocilj A, Albrecht R, Yonath A, Franceschi F. Nature 2001; 413: 814
2b Tenson T, Lovmar M, Ehrenberg M. J. Mol. Biol. 2003; 330: 1005

3 Kirillov S, Porse BT, Vester B, Woolley P, Garett R. FEBS Lett. 1997; 406: 223
4 Mason DJ, Dietz A, De Boer C.. Antimicrob. Agents Chemother. 1962; 554
5 Sztarricskai F, Batta G, Dinya G, Hornyak M, Roth E. J. Antibiot. 1999; 52: 1050

6a Schroeder W, Bannister B, Hoeksema H. J. Am. Chem. Soc. 1967; 89: 2448
6b Sztarricskai F, Dinya Z, Batta G, Masuma R, Omura S. Magy Kem. Foly., Kem. Kozl. 1997; 103: 524
6c Collin M.-P, Hobbie SN, Bottger EC, Vasella A. Helv. Chim. Acta 2008; 91: 1838
6d Argoudelis AD, Coats JH, Mason DJ, Sebek OK. J. Antibiot. 1969; 22: 309
6e Magerlein BJ, Kagan F. J. Med. Chem. 1969; 12: 780
6f Magerlein BJ. J. Med. Chem. 1972; 15: 1255
6g Birkenmeyer RD, Kroll SJ, Lewis C, Stern KF, Zurenko GE. J. Med. Chem. 1984; 27: 216
6h Pospisil S, Sedmera P, Halada P, Havlicek L, Spizek J. Tetrahedron Lett. 2004; 45: 2943

7a Sztarricskai F, Dinya G, Batta A, Mocsrai M, Hollosi Z, Majer R, Masuma R, Omura S. J. Antibiot. 1997; 50: 866
7b Collin M.-P, Hobbie SN, Bottger EC, Vasella A. Helv. Chim. Acta 2009; 92: 230

8 Hanessian S, Kothakonda KK. Bioorg. Med. Chem. 2005; 13: 5283

9a Umemura E, Wakiyama Y, Kumura K, Ueda K, Masaki S, Watanabe T, Yamamoto M, Hirai Y, Fushimi H, Yoshida T, Ajito K. J. Antibiot. 2013; 66: 195
9b Umemura E, Kumura K, Masaki S, Ueda K, Wakiyama Y, Sato Y, Yamamoto M, Ajito K, Watanabe T, Kaji C. US 20100184746A1, 2010
9c Lewis J, Patel DV, Kumar AS, Gordeev MF. WO 2004016632 A2
9d Sztaricskai F, Dinya Z, Puskaa MM, Batta G, Masuma R, Omura S. J. Antibiot. 1996; 49: 941

10a Osono T, Umezawa H. J. Antimicrob. Chemother. 1985; 16: 151
10b Magerlein BJ, Birkenmeyer RD, Kagan F. Antimicrob. Agents Chemother. 1966; 727
10c Birkenmeyer RD, Kagan F. J. Med. Chem. 1970; 13 : 616

11 Hirai Y, Maebashi K, Yamada K, Wakiyama Y, Kumura K, Umemura E, Ajito K. J. Antibiot. 2021; 74: 124
12 Mitcheltree MJ, Pisipati A, Syroegin EA, Silvestre KJ, Klepacki D, Mason JD, Terwilliger DW, Testolin G, Pote AR, Wu KJ. Y, Ladley RP, Chatman K, Mankin AS, Polikanov YS, Myers AG. Nature 2021; 599: 507
13 Mitcheltree MJ, Stevenson JW, Pisipati A, Myers AG. J. Am. Chem. Soc. 2021; 143: 6829
14 Mason JD, Terwilliger DW, Pote AR, Myers AG. J. Am. Chem. Soc. 2021; 143: 11019

15a Bauman AC, Broderick JC, Dacus RM. IV, Grover DA, Trzupek LS. Tetrahedron Lett. 1993; 34: 7019
15b DeGrado WF, Kaiser ET. J. Org. Chem. 1980; 45: 1295
15c DeGrado WF, Kaiser ET. J. Org. Chem. 1982; 47: 3258

16a Bérubé C, Gagnon D, Borgia A, Richard D, Voyer N. Chem. Commun. 2019; 55: 7434
16b Bérubé C, Borgia A, Voyer N. Org. Biomol. Chem. 2018; 16: 9117
16c Voyer N, Lavoie A, Pinette M, Bernier J. Tetrahedron Lett. 1994; 35: 355

17 Tremblay T, Robert-Scott G, Bérubé C, Carpentier A, Voyer N, Giguère D. Chem. Commun. 2019; 55: 13741

18a Ramesh R, Sonawane S, Reddy DS, Bandichhor R. Protecting-Group-Free Synthesis of Drugs and Pharmaceuticals . In Protecting-Group-Free Organic Synthesis . Fernandes RA. Wiley; Hoboken: 2018: 155-181
18b Young IS, Baran PS. Nat. Chem. 2009; 1: 193
18c Trost BM. Science 1991; 254: 1471
18d Wender PA, Verma VA, Paxton TJ, Pillow TH. Acc. Chem. Res. 2008; 41: 40

19a Bérubé C, Borgia A, Gagnon D, Mukherjee A, Richard D, Voyer N. J. Nat. Prod. 2020; 83: 1778
19b Smith RA, Bobko MA, Lee W. Bioorg. Med. Chem. Lett. 1998; 8: 2369

20a Cordero-Vargas A, Sartillo-Piscil F. Protecting-Group-Free Synthesis in Carbohydrate Chemistry. In Protecting-Group-Free Organic Synthesis . Fernandes RA. Wiley; Hoboken: 2018: 183-200
20b Tanaka T. Protecting-Group-Free Synthesis of Glycosyl Derivatives, Glycopolymers, and Glycocojugates. In Protecting-Group-Free Organic Synthesis. Fernandes RA. Wiley; Hoboken: 2018: 201-228
20c Vasicek T, Spiwok V, Cerveny J, Petraskova L, Bumba L, Vrbata D, Pelantova H, Kren V, Bojarova P. Chem. Eur. J. 2020; 26: 9620
20d Dussouy C, Téletchéa S, Lambert A, Charlier C, Botez I, De Ceuninck F, Grandjean C. J. Org. Chem. 2020; 85: 16099
20e Tejler J, Leffler H, Nilsson UJ. Bioorg. Med. Chem. Lett. 2005; 15: 2343
20f Bergh A, Leffler H, Sundin A, Nilsson UJ, Kann N. Tetrahedron 2006; 62: 8309

21 St-Gelais J, Giguère D. Synthesis 2021; 53: 3735
22 Cheng JM. H, Chee SH, Knight DA, Acha-Orbea H, Hermans IF, Timmer MS. M, Stocker BL. Carbohydr. Res. 2011; 346: 914
23 Typical Experimental Procedure for the Cleavage of Oxime Resin To a peptide synthesis vessel was added the oxime resin (1.1 mmol g^–1, 1.25 equiv) and was swelled with CH₂Cl₂ (3 × 5 mL). To a solution of the oxime resin in CH₂Cl₂/DMF (8:2, 0.02 M) were added amino sugar (1 equiv) and DIPEA (2.5 equiv). The vessel was mechanically stirred for a few seconds, and acetic acid (5 equiv) was added to the mixture. The peptide synthesis vessel was mechanically stirred at room temperature until starting material was consumed (overnight). The content of the vessel was then collected in a flask and the resin was washed with CH₂Cl₂ (3 × 5 mL) and MeOH (3 × 5 mL). The organic phase was concentrated under reduced pressure, and the resulting crude was purified by flash column chromatography. Characterization Data for S-Methyl 6-Deoxy-6-{[N-(N-acetyl)-glycinyl]}-l-leucylamido-α-thiolincosaminide (10) R_f = 0.49 (silica, MeOH/DCM, 1:4); [α]_D ²⁵ 96.2 (c 0.3, MeOH). IR (ATR, diamond): ν = 3307, 1659, 1642, 1285, 1075, 1049 cm^–1. ¹H NMR (500 MHz, D₂O): δ = 5.35 (d, ³ J _H1–H2 = 5.8 Hz, 1 H, H1), 4.34 (dd, ³ J _{CHαLeu–CH2αβLeu} = 9.8 Hz, ³ J _{CHαLeu-CH2αβLeu} = 5.0 Hz, 1 H, CHαLeu), 4.29 (dd, ³ J _H6–H5 = 9.7 Hz, ³ J _H6–H7 = 4.5 Hz, 1 H, H6), 4.23 (dd, ³ J _H5–H6 = 9.7 Hz, ³ J _H5–H4 = 1.2 Hz, 1 H, H5), 4.111 (qd, ³ J _H7–H8a = ³ J _H7–H8b = ³ J _H7–H8c = 6.5 Hz, ³ J _H7–H6 = 4.5 Hz, 1 H, H7), 4.095 (dd, ³ J _H2–H3 = 10.2 Hz, ³ J _H2–H1 = 5.7 Hz, 1 H, H2), 3.93 (dd, ³ J _H4–H3 = 3.2 Hz, ³ J _H4–H5 = 1.2 Hz, 1 H, H4), 3.89 (d, ² J _{CH2aGly–CH2bGly} = 17.0 Hz, 1 H, CH₂bGly), 3.64 (dd, ³ J _H3–H2 = 10.4 Hz, ³ J _H3–H4 = 3.2 Hz, 1 H, H3), 2.13 (s, 3 H, SCH₃), 2.05 (s, 3 H, COCH₃), 1.71–1.57 (m, 3 H, CH₂βLeu, CHγLeu), 1.13 (d, ³ J _CH3(8)–H7 = 6.5 Hz, 3 H, CH₃(8)), 0.94 (d, ³ J _{CH3δ1Leu–CHγLeu} = 6.1 Hz, 1 H, CH₃δ1Leu), 0.88 (d, ³ J _{CH3δ2Leu–CHγLeu} = 6.1 Hz, 1 H, CH₃δ2Leu) ppm. ¹³C NMR (126 MHz, D₂O): δ = 174.9, 174.8, 171.7 (3 C, 3 × CO), 88.0 (1 C, C1), 70.2 (1 C, C3), 69.4 (1 C, C5), 68.3 (1 C, C4), 67.6 (1 C, C2), 66.7 (1 C, C7), 53.1 (1 C, C6), 52.7 (1 C, CHαLeu), 42.4 (1 C, CH₂Gly), 39.6 (1 C, CH₂βLeu), 24.2 (1 C, CH₂γLeu), 22.0 (1 C, CH₃δ1Leu), 21.6 (1 C, COCH₃), 20.5 (1 C, CH₃δbLeu), 15.9 (1 C, C8), 12.8 (1 C, SCH₃) ppm. HRMS (ESI) m/z [M + H]⁺ calcd for C₁₉H₃₆N₃O₈S⁺: 466.2218; found: 466.2209. Characterization Data for S-Methyl 6-Deoxy-6-{[N-(N-tert-butoxycarbonyl)-l-phenylalanyl]-l-alanylamido}-α-thiolincosaminide (11) R_f = 0.32 (silica, MeOH/DCM, 1:9); [α]_D ²⁵ 120.4 (c 0.4, MeOH). IR (ATR, diamond): ν = 3333, 2926, 1691, 1631, 1530, 1168, 1050 cm^–1. ¹H NMR (500 MHz, CD₃OD): δ = 7.31–7.19 (m, 5 H, Ar–Phe), 5.26 (d, ³ J _H1–H2 = 5.6 Hz, 1 H, H1), 4.33 (q, ³ J _{CHαPhe–CH3aAla} = ³ J _{CHαPhe–CH3bAla} = ³ J _{CHαPhe–CH3cAla} = 7.3 Hz, 1 H, CHαAla), 4.32 (dd, ³ J _{CHαPhe–CH2bPhe} = 9.9 Hz, ³ J _{CHαPhe–CH2aPhe} = 4.7 Hz, 1 H, CHαPhe), 4.25–4.18 (m, 2 H, H5, H6), 4.09 (dd, ³ J _H2–H3 = 10.1 Hz, ³ J _H2–H1 = 5.6 Hz, 1 H, H2), 4.00 (p, ³ J _H7–H8a = ³ J _H7–H8b = ³ J _H7–H8b = ³ J _H7–H6 = 6.2 Hz, 1 H, H7), 3.95 (d, ³ J _H4–H3 = 3.4 Hz, 1 H, H4), 3.56 (dd, ³ J _H3–H2 = 10.2 Hz, ³ J _H3–H4 = 3.4 Hz, 1 H, H3), 3.16 (dd, ² J _{CH2aPhe–CH2bPhe} = 13.9 Hz, ³ J _{CH2aPhe–CHαPhe} = 4.7 Hz, 1 H, CH₂aPhe), 2.80 (dd, ² J _{CH2bPhe–CH2aPhe} = 14.1 Hz, ³ J _{CH2bPhe–CHαPhe} = 9.9 Hz, 1 H, CH₂bPhe), 2.10 (s, 3 H, SCH₃), 1.39 (d, ³ J _{CH3Ala–CHαAla} = 7.3 Hz, 3 H, CH₃Ala), 1.35 (s, 9 H, C(CH₃)₃), 1.19 (d, ³ J _C _H3 _(8)–H7 = 6.4 Hz, 3 H, CH₃(8)) ppm. ¹³C NMR (126 MHz, CD₃OD): δ = 175.7, 174.5, 157.8 (3 C, 3 × CO), 138.7, 130.4, 129.4, 127.7 (6 C, Ar–Phe), 89.9 (1 C, C1), 80.7 (1 C, C(CH₃)₃), 71.9 (1 C, C3), 70.8 (1 C, C5), 70.4 (1 C, C4), 69.5 (1 C, C2), 68.1 (1 C, C7), 57.2 (1 C, CHαPhe), 55.8 (1 C, C6), 50.9 (1 C, CHαAla), 39.1 (1 C, CH₂Phe), 28.7 (3 C, C(CH₃)₃), 18.5 (1 C, C8), 17.9 (1 C, CH₃Ala), 13.6 (1 C, SCH₃) ppm. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₆H₄₂N₃O₉S⁺: 572.2636; found: 572.2640.

Supplementary Material

Supporting Information