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DOI: 10.1055/a-1672-3000
First Total Synthesis of the Marine-Derived Anti-inflammatory Natural Product (–)-Herdmanine D through a Steglich Esterification
The authors are grateful to SERB, Department of Science and Technology, India, for providing financial support (Sanction order no. SB/S1/OC-91/2013)
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Abstract
An efficient and regioselective route for the first total synthesis of the antiinflammatory marine natural product (–)-herdmanine D, with an excellent overall yield of 18%, is described. A key feature of the synthetic strategy is a Steglich esterification of regioselectively constructed 6-bromo-5-methoxy-1H-indole-3-carboxylic acid with protected l-tyrosine. The formation of the l-isomer was confirmed through measurement of the optical activity. The current strategy paves the way for the construction of diverse analogues of (–)-herdmanine D for drug development.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-1672-3000.
- Supporting Information
Publikationsverlauf
Eingereicht: 07. September 2021
Angenommen nach Revision: 18. Oktober 2021
Accepted Manuscript online:
19. Oktober 2021
Artikel online veröffentlicht:
11. November 2021
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References and Notes
- 1a Jiménez C. ACS Med. Chem. Lett. 2018; 9: 959
- 1b Carroll AR, Copp BR, Davis RA, Keyzers RA, Prinsep MR. Nat. Prod. Rep. 2020; 37: 175
- 1c Shinde P, Banerjee P, Mandhare A. Expert Opin. Ther. Pat. 2019; 29: 283
- 2a Dou X, Dong B. Mar. Drugs 2019; 17: 670
- 2b Palanisamy SK, Rajendran NM, Marino A. Nat. Prod. Bioprospect. 2017; 7: 1
- 2c Arumugam V, Venkatesan M, Ramachandran S, Sundaresan U. Int. J. Pept. Res. Ther. 2018; 24: 13
- 3a Watters DJ. Mar. Drugs 2018; 16: 162
- 3b Arumugam V, Venkatesan M, Ramachandran K, Sundaresan U, Ramachandran S. Encyclopedia of Marine Biotechnology . Kim S.-K. Wiley Blackwell; Chichester: 2020. Chap. 113 DOI: 10.1002/9781119143802.ch113
- 3c Menna M, Fattorusso E, Imperatore C. Molecules 2011; 16: 8694
- 3d Mauro M, Lazzara V, Punginelli D, Arizza V, Vazzana M. Dev. Comp. Immunol. 2020; 108: 103669
- 3e Dumollard R, Gazo I, Gomes ID. L, Besnardeau L, McDougall A. Curr. Topics Med. Chem (Sharjah, United Arab Emirates) 2017; 17: 2056
- 4 Blunt JW, Copp BR, Keyzers RA, Munro MH, Prinsep MR. Nat. Prod. Rep. 2015; 32: 116
- 5 Agrawal S, Acharya D, Adholeya A, Barrow CJ, Deshmukh SK. Front. Pharmacol. 2017; 8: 828
- 6 Rangel M, de Barcellos Falkenberg M. J. Coastal. Life Med. 2015; 3: 421
- 7a Cheng J, Li R, Lin G. Youji Huaxue 1995; 15: 445
- 7b Li JL, Han SC, Yoo ES, Shin S, Hong J, Cui Z, Li H, Jung JH. J. Nat. Prod. 2011; 74: 1792
- 7c Li JL, Xiao B, Park M, Yoo ES, Shin S, Hong J, Chung HY, Kim HS, Jung JH. J. Nat. Prod. 2012; 75: 2082
- 8 Sharma P, Sharma N, Kashyap G, Bhagat S. Synth. Commun. 2020; 50: 719
- 9 (–)-Herdmanine D A solution of LiOH (0.13 g, 5.0 equiv) in H2O (2 mL) was added slowly to a stirred solution of ester 7 (0.5 g, 1.0 equiv) in MeOH (2 mL), and the mixture was stirred for 4 h at rt. When the reaction was complete (TLC), the mixture was concentrated under reduced pressure and acidified with 1 N aq HCl to pH 2. The solid that precipitated was collected by filtration on a sintered funnel, washed with ice-cold H2O, and then dried under a high vacuum to give a light-brown solid; yield: 0.18 g (41%); mp 210–215 °C; [α]D 23 –20.3. 1H NMR (400 MHz, DMSO-d 6): δ = 12.96 (br s, 1 H, –COOH), 12.36 (br s, 1 H, –NH), 9.22 (s, 1 H), 8.76 (s, 1 H), 8.46–8.43 (d, J = 9 Hz, 2 H), 7.83 (s, 1 H), 7.65–7.63 (d, J = 6 Hz, 2 H), 7.37–7.35 (d, J = 6 Hz, 2 H). 4.02–3.94 (m, 1 H), 2.79–2.75 (m, 2 H). 13C NMR (100 MHz, DMSO-d 6): δ = 176.47, 164.72, 149.21, 140.54, 136.99, 132.84, 129.65, 127.44, 123.74, 120.54, 117.34, 111.51, 108.30, 106.89, 104.67, 103.70, 57.38, 36.88. HRMS (ESI): m/z [M + H]+ calcd for C18H15BrN2O5: 418.0164; found: 418.0170.