Scalable Synthesis of l-allo-Enduracididine: The Unusual Amino Acid Present in Teixobactin

Abstract

A scalable synthesis of l-allo-enduracididine is achieved from commercially available (S)-glycidol in ten linear steps involving well-established synthetic transformations. The synthetic route is flexible and can be used to synthesize all four diastereomers by changing the stereochemistry of glycidol and Sharpless asymmetric dihydroxylation reagent.

Key words

antibiotics - teixobactin - depsipeptide - unusual amino acid - l-allo-enduracididine - Staudinger reaction - Sharpless asymmetric dihydroxylation

Publication History

Received: 18 May 2021

Accepted after revision: 13 June 2021

Accepted Manuscript online:
13 June 2021

Article published online:
01 July 2021

• References and Notes

• 1a Willyard C. Nature 2017; 543: 7643
• 1b Arias CA, Murray BE. N. Engl. J. Med. 2015; 372: 1168
• 1c Zhen X, Lundborg CS, Sun X, Hu X, Dong H. Antimicrob. Resist. Infect. Control 2019; 8: 137
• 1d Mulani MS, Kamble EE, Kumkar SN, Tawre MS, Pardesi KR. Front. Microbiol. 2019; 10: 539
• 2 Ling LL, Schneider T, Peoples AJ, Spoering AL, Engels I, Conlon BP, Mueller A, Schaeberle TF, Hughes DE, Epstein S, Jones M, Lazarides L, Steadman VA, Cohen DR, Felix CR, Fetterman KA, Millett WP, Nitti AG, Zullo AM, Chen C, Lewis K. Nature 2015; 517: 455
• 3 Ng V, Chan WC. Chem. Eur. J. 2016; 22: 12606
• 4 Atkinson DJ, Naysmith BJ, Furkert DP, Brimble MA. Beilstein J. Org. Chem. 2016; 12: 2325
• 5 Giltrap AM, Dowman LJ, Nagalingam G, Ochoa JL, Linington RG, Britton WJ, Payne RJ. Org. Lett. 2016; 18: 2788
• 6 Jin K, Sam LH, Po KH. L, Lin D, Zadeh EH. G, Chen S, Yuan Y, Li X. Nat. Commun. 2016; 7: 12394
• 7 Liu L, Wu S, Wang Q, Zhang M, Wang B, He G, Chen G. Org. Chem. Front. 2018; 5: 1431
• 8 Gao B, Chen S, Hou YN, Zhao YJ, Ye T, Xu Z. Org. Biomol. Chem. 2019; 17: 1141
• 9 Zong Y, Fang F, Meyer KJ, Wang L, Ni Z, Gao H, Lewis K, Zhang J, Rao Y. Nat. Commun. 2019; 10: 3268
• 10a Jad YE, Acosta GA, Naicker T, Ramtahal M, El-Faham A, Govender T, De la Torre BG, Albericio F. Org. Lett. 2015; 17: 6182
• 10b Parmar A, Iyer A, Vincent CS, Van Lysebetten D, Prior SH, Madder A, Taylor EJ, Singh I. Chem. Commun. 2016; 52: 6060
• 10c Yang H, Chen KH, Nowick JS. ACS Chem. Biol. 2016; 11: 1823
• 10d Monaim SA. H. A, Jad YE, Acosta GA, Naicker T, Ramchuran EJ, El-Faham A, Govender T, Kruger HG, De la Torre BG, Albericio F. RSC Adv. 2016; 6: 73827
• 10e Monaim SA. H. A, Jad YE, Ramchuran EJ, El-Faham A, Govender T, Kruger HG, De la Torre BG, Albericio F. ACS Omega 2016; 1: 1262
• 10f Monaim SA. H. A, Noki S, Ramchuran EJ, El-Faham A, Albericio F, De la Torre BG. Molecules 2017; 22: 1632
• 10g Monaim SA. H. A, Ramchuran EJ, El-Faham A, Albericio F, De la Torre BG. J. Med. Chem. 2017; 60: 7476
• 10h Wu C, Pan Z, Yao G, Wang W, Fang L, Su W. RSC Adv. 2017; 7: 1923
• 10i Jin K, Po KH. L, Wang S, Reuven JA, Wai CN, Lau HT, Chan TH, Chen S, Li X. Bioorg. Med. Chem. 2017; 25: 4990
• 10j Parmar A, Iyer A, Lloyd DG, Vincent CS, Prior SH, Madder A, Taylor EJ, Singh I. Chem. Commun. 2017; 53: 7788
• 10k Parmar A, Iyer A, Prior SH, Lloyd DG, Goh ET. L, Vincent CS, Pallag TP, Bachrati CZ, Breukink E, Madder A, Lakshminarayanan R, Taylor EJ, Singh I. Chem. Sci. 2017; 8: 8183
• 10l Schumacher CE, Harris PW. R, Ding X.-B, Krause B, Wright TH, Cook GM, Furkert DP, Brimble MA. Org. Biomol. Chem. 2017; 15: 8755
• 10m Ng V, Kuehne SA, Chan WC. Chem. Eur. J. 2018; 24: 9136
• 10n Parmar A, Lakshminarayanan R, Iyer A, Mayandi V, Goh ET. L, Lloyd DG, Chalasani ML. S, Verma NK, Prior SH, Beuerman RW, Madder A, Taylor EJ, Singh I. J. Med. Chem. 2018; 61: 2009
• 11a Parmar A, Prior SH, Iyer A, Vincent CS, Van Lysebetten D, Breukink E, Madder A, Taylor EJ, Singh I. Chem. Commun. 2017; 53: 2016
• 11b Yang H, Du Bois DR, Ziller JW, Nowick JS. Chem. Commun. 2017; 53: 2772
• 11c Chen KH, Le SP, Han X, Frias JM, Nowick JS. Chem. Commun. 2017; 53: 11357
• 11d Yang H, Wierzbicki M, Du Bois DR, Nowick JS. J. Am. Chem. Soc. 2018; 140: 14028
• 11e Monaim SA. H. A, Jad YE, El-Faham A, De la Torre BG, Albericio F. Bioorg. Med. Chem. 2018; 26: 2788
• 11f Yang H, Pishenko AV, Li X, Nowick JS. J. Org. Chem. 2020; 85: 1331
• 11g Gunjal VB, Thakare R, Chopra S, Reddy DS. J. Med. Chem. 2020; 63: 12171
• 12 Dhara S, Gunjal VB, Handore KL, Reddy DS. Eur. J. Org. Chem. 2016; 4289
• 13a Rudolph J, Hannig F, Theis H, Wischnat R. Org. Lett. 2001; 3: 3153
• 13b Peoples AJ, Hughes D, Ling LL, Millett W, Nitti A, Spoering A, Steadman VA, Chiva JY. C, Lazarides L, Jones MK, Poullence KG, Lewis K. WO2014089053 2014
• 13c Peoples, A. J.; Hughes, D.; Ling, L. L.; Millett, W.; Nitti, A.; Spoering, A.; Steadman, V. A.; Chiva, J. Y. C.; Lazarides, L.; Jones, M. K.; Poullence, K. G.; Lewis, K. US20140194345, 2014.
• 14 Craig W, Chen J, Richardson D, Thorpe R, Yuan Y. Org. Lett. 2015; 17: 4620
• 15a Sangeetha D, Nayani K, Mainkar PS, Chandrasekhar S. Synlett 2019; 30: 2268
• 15b Bukya H, Nayani K, Gangireddy P, Mainkar PS. Eur. J. Org. Chem. 2020; 5358
• 16 Carneiro VM. T, Avila CM, Balunas MJ, Gerwick WH, Pilli RA. J. Org. Chem. 2014; 79: 630
• 17 Bonini C, Chiummiento L, Lopardo MT, Pullez M, Colobert F, Solladie G. Tetrahedron Lett. 2003; 44: 2695
• 18a Sharpless KB, Amberg W, Bennani YL, Crispino GA, Hartung J, Jeong KS, Kwong HL, Morikawa K, Wang ZM, Xu D, Zhang X.-L. J. Org. Chem. 1992; 57: 2768
• 18b Kolb HC, Sharpless KB. Chem Rev. 1994; 94: 2483
• 19a Austad BA, Calkins TL, Fang FG, Horstmann TE, Hu Y, Lewis BM, Niu X, Noland TA, Orr JD, Schnaderbeck MJ, Zhang H, Asakawa N, Asai N, Chiba H, Hasebe T, Hoshino Y, Ishizuka H, Kajima T, Kayano A, Komatsu Y, Kubota M, Kuroda H, Miyazawa M, Tagami K, Watanabe T. Synlett 2013; 24: 333
• 19b Sun D.-Y, Han G.-Y, Gong J.-X, Nay B, Li X.-W, Guo Y.-W. Org. Lett. 2017; 19: 714
• 20 Synthetic Procedure for Guanidine Derivative 3 Triphenylphosphine (2.0 g, 7.2 mmol) was added to a stirred solution of azide 8 (1.27 g, 2.5 mmol) in THF–H₂O (15 mL, 3:1) at 0 °C. Then the reaction was allowed to warm to room temperature and stirred for 12 h. After this period, to the reaction Goodman’s reagent (N,N'-di-Cbz-1H-pyrazole-1-carboxamidine, 968 mg, 2.5 mmol) was added, and the mixture was stirred for another 6 h. The reaction was extracted with EtOAc (2 × 100 mL), the organic layer was washed with brine (75 mL), dried over anhydrous Na₂SO₄, and concentrated under vacuum. The residue was purified by column chromatography on silica gel using 85:15 hexanes–EtOAc (v/v) as eluent to give 3 (1.7 g, 85%) as a white solid. TLC: R_f = 0.5 (hexanes–EtOAc, 7:3); mp 92 °C; [α]_D ²⁰ +6.2 (c 1.1, CHCl₃). IR (neat): ν_max = 3370, 3334, 2946, 1640, 1057 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 11.65 (s, 1 H), 8.71–8.68 (br s, 1 H), 7.57–7.50 (m, 4 H), 7.40–7.16 (m, 16 H), 5.10 (s, 2 H), 5.04 (s, 2 H), 4.82 (d, J = 8.8 Hz, 1 H), 4.55 (s, 1 H), 3.86–3.75 (m, 1 H), 3.75–3.59 (m, 3 H), 3.51 (dd, J = 10.3, 3.7 Hz, 1 H), 3.23–3.08 (m, 1 H), 1.65–1.53 (m, 1 H), 1.37 (s, 9 H), 1.35–1.25 (m, 1 H), 0.98 (s, 9 H). ¹³C NMR (101 MHz, CDCl₃): δ = 163.6, 157.3, 156.1, 153.5, 136.7, 135.6, 135.5, 134.6, 132.9, 132.7, 129.9, 129.8, 128.6, 128.5, 128.4, 128.3, 128.1, 127.8, 127.8, 80.1, 68.0, 67.0, 66.3, 48.6, 46.3, 38.1, 28.3, 26.8, 19.2. HRMS (ESI): m/z calcd for [M + H]⁺: C₄₃H₅₅N₄O₈Si: 783.3779; found: 783.3783.
• 21 Synthetic Procedure for Intramolecular Cyclization of Guanidine Derivative 3; (S)-Benzyl-2-{[(benzyloxy)carbonyl]imino}-5-{(S)-2-[(tert-butoxycarbonyl)amino]-3-[(tert-butyl diphenylsilyl)oxy]propyl}imidazolidine-1-carboxylate (9) To a solution of 3 (3.2 g, 4 mmol) in anhydrous CH₂Cl₂ (20 mL) was added DIPEA (3.6 mL, 20 mmol), followed by Tf₂O (0.76 mL, 4.5 mmol) dropwise at –78 °C under nitrogen atmosphere. After stirring for 1 h, the reaction was quenched by the addition of ammonium chloride (100 mL), the two layers were separated, and the aqueous layer was extracted with CH₂Cl₂ (100 mL). The combined organic layer was washed with brine (50 mL), dried over anhydrous Na₂SO₄, and concentrated under vacuum to give a colorless oil. The residue was purified by column chromatography on silica gel using 70:30 hexanes–EtOAc (v/v) as eluent to give 9 (2.81 g, 90%) as a white solid. TLC: R_f = 0.5 (hexanes–EtOAc, 1:1); mp 84 °C; [α]_D ²⁰ –7.5 (c 1.0, CHCl₃). IR (neat): ν_max = 3758, 3709, 3481, 3367, 2940, 1710, 1259, 1159 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 8.82–8.41 (br s, 1 H), 7.63–7.52 (m, 4 H), 7.47–7.27 (m, 16 H), 5.27 (s, 2 H), 5.16 (q, J = 12.4 Hz, 2 H), 4.63 (d, J = 8.9 Hz, 1 H), 4.34 (t, J = 8.4 Hz, 1 H), 3.79 (t, J = 8.4 Hz, 1 H), 3.72–3.60 (m, 2 H), 3.52 (dd, J = 9.9, 3.4 Hz, 1 H), 3.43 (d, J = 9.5 Hz, 1 H), 2.07 (t, J = 12.0 Hz, 1 H), 1.63 (t, J = 11.8 Hz, 1 H), 1.43 (s, 9 H), 1.01 (s, 9 H). ¹³C NMR (126 MHz, CDCl₃): δ = 156.0, 135.6, 135.6, 135.3, 133.1, 132.9, 130.1, 130.0, 128.8, 128.4, 128.2, 128.0, 127.9, 79.8, 68.4, 67.5, 66.5, 54.0, 48.7, 36.1, 28.5, 26.9, 19.3. HRMS (ESI): m/z calcd for [M + H]⁺: C₄₃H₅₃N₄O₇Si: 765.3662; found: 765.3678.