Stereoselective Synthesis of Acyclic Skeleton of Boscartin A

Abstract

Stereoselective synthesis of key acyclic skeleton of structurally challenging and biologically active boscartin A possessing six stereogenic centers, among which three are tertiary, has been achieved for the first time. The synthetic study comprises the Sharpless asymmetric epoxidation (SAE) followed by stereoselective epoxide opening for installation of C-11 and C-12 centers, Meyer–Schuster rearrangement followed by intramolecular oxa-Michael addition for construction of C-1 center, SAE followed by CBS reduction and subsequent cycloetherification for stereoselective generation of C-3, C-4, and C-7 centers, Gilman reaction for introduction of C-9 olefin and Grignard reaction for installation of C-8 olefin.

Key words

stereoselective synthesis - Sharpless asymmetric epoxidation - boscartin A

Publication History

Received: 21 July 2022

Accepted after revision: 22 August 2022

Accepted Manuscript online:
22 August 2022

Article published online:
21 September 2022

• References and Notes

• 1a Blunt JW, Copp BR, Keyzers RA, Munroa MH. G, Prinsep MR. Nat. Prod. Rep. 2013; 30: 237
• 1b Blunt JW, Copp BR, Keyzers RA, Munroa MH. G, Prinsep MR. Nat. Prod. Rep. 2014; 31: 160
• 1c Martins AH, Hu J, Xu Z, Mu C, Alvarez P, Ford BD, Sayed KE, Eterovic VA, Ferchmin PA, Hao J. Neuroscience 2015; 291: 250
• 1d Jia R, Guo YW, Mollo E, Gavagnin M, Cimino G. J. Nat. Prod. 2006; 69: 819
• 1e Duh CY, Wang SK, Tseng HK, Sheu JH, Chiang MY. J. Nat. Prod. 1998; 61: 844
• 1f Wen T, Ding Y, Deng Z, Ofwegen L, Proksch P, Lin W. J. Nat. Prod. 2008; 71: 1133
• 2 Ren J, Wang YG, Wang AG, Wu LQ, Zhang HJ, Wang WJ, Su YL, Qin HL. J. Nat. Prod. 2015; 78: 2322
• 3 Matsuzawa A, Shiraiwa J, Kasamatsu A, Sugita K. Org. Lett. 2018; 20: 1031
• 4a Mandal GH, Saha D, Goswami RK. Org. Biomol. Chem. 2020; 18: 2346
• 4b Saha D, Guchhait S, Goswami RK. Org. Lett. 2020; 22: 745
• 4c Paul D, Saha S, Goswami RK. Org. Lett. 2018; 20: 4606
• 4d Chatterjee S, Guchhait S, Goswami RK. J. Org. Chem. 2014; 79: 7689
• 4e Guchhait S, Chatterjee S, Ampapathi RS, Goswami RK. J. Org. Chem. 2017; 82: 2414
• 5a Kumar VP, Chandrasekhar S. Org. Lett. 2013; 15: 3610
• 5b González IC, Forsyth CJ. J. Am. Chem. Soc. 2000; 122: 9099
• 6a Shen M, Kretschmer M, Brill ZG, Snyder SA. Org. Lett. 2016; 18: 5018
• 6b Ghosh S, Kumar SU, Shashidhar J. J. Org. Chem. 2008; 73: 1582
• 6c Dias LC, Melgar GZ, Jardim LS. A. Tetrahedron Lett. 2005; 46: 4427
• 7a Engel DA, Lopez SS, Dudley GB. Tetrahedron 2008; 64: 6988
• 7b Engel DA, Dudley GB. Org. Biomol. Chem. 2009; 7: 4149
• 7c Liu J, Zhou L, Zou Y, Wang Q, Goeke A. Org. Biomol. Chem. 2020; 18: 7832
• 8a Armstrong A, Pyrkotis C. Tetrahedron Lett. 2009; 50: 3325
• 8b Bates RH, Shotwell JB, Roush WR. Org. Lett. 2008; 10: 4343
• 9a Ogura Y, Sato H, Kuwahara S. Org. Lett. 2016; 18: 2399
• 9b Yadav JS, Dutta P. J. Org. Chem. 2016; 81: 1786
• 9c Kuilya TK, Das S, Saha D, Goswami RK. Org. Biomol. Chem. 2018; 16: 7595
• 9d Ogura Y, Sato H, Kuwahara S. Org. Lett. 2016; 18: 2399
• 10a Ohtani I, Kusumi T, Kashman Y, Kakisawa H. J. Am. Chem. Soc. 1991; 113: 4092
• 10b Seco JM, Quinoa E, Riguera R. Chem. Rev. 2004; 104: 17
• 11 Dhimitruka I, SantaLucia J. Org. Lett. 2006; 8: 47
• 12a Morimoto Y, Okita T, Kambara H. Angew. Chem. Int. Ed. 2009; 48: 2538
• 12b Busch T, Dräger G, Kunst E, Benson H, Sasse F, Siems K, Kirschning A. Org. Biomol. Chem. 2016; 14: 9040
• 12c Kodama T, Aoki S, Kikuchi S, Matsuo T, Tachi Y, Nishikawa K, Morimoto Y. Tetrahedron Lett. 2013; 54: 5647
• 13a Alam M, Wise C, Baxter CA, Cleator E, Walkinshaw A. Org. Process Res. Dev. 2012; 16: 435
• 13b Huynh C, Boumechal FD, Linstrumelle G. Tetrahedron Lett. 1979; 20: 1503
• 14 General Experimental Procedure All moisture-sensitive reactions were performed in oven- or flame-dried glassware with Teflon-coated magnetic stirring bar under argon atmosphere using dry, freshly distilled solvents. Air- and moisture-sensitive liquids were transferred via a gastight syringe and a stainless-steel needle. Reactions were monitored by thin-layer chromatography (TLC, silica gel 60 F254) plates with UV light, ethanolic anisaldehyde (with 1% AcOH and 3.3% concd H₂SO₄), heat, and aqueous KMnO₄ (with K₂CO₃ and 10% aqueous NaOH solution) as developing agents. All workup and purification procedures were carried out with reagent-grade solvents under ambient atmosphere unless otherwise stated. Column chromatography was performed using silica gel 60–120 mesh, 100–200 mesh, and 230–400 mesh. Yields mentioned as chromatographically and spectroscopically homogeneous materials unless otherwise stated. Optical rotations were measured only for pure compounds and not for mixtures using sodium (589, D line; Anton Paar MCP 200 system) lamp and are reported as follows: [α]_D ²⁵ (c = g/100 mL, solvent). IR spectra were recorded as neat (for liquids). HRMS were taken using Quadruple-TOF (Q-TOF) micro-MS system using electrospray ionization (ESI) technique. NMR spectra were recorded on 300, 400, 500, and 600 MHz and ¹³C and 2D NMR spectra were recorded on 75 and 150 MHz spectrometers in appropriate solvents and the chemical shifts are shown in ppm scales. 3-[(2R,3R)-3-{[(2S,5R)-5-{(S)-2-(Benzyloxy)-1-[(tert-butyldimethylsilyl)oxy]ethyl}-2-isopropyl-5-methyltetrahydrofuran-2-yl]methyl}-2-methyloxiran-2-yl]propan-1-ol (12) Colorless liquid; yield 80%. R_f = 0.35 (20% EtOAc/hexane); [α]_D ²⁵ +12.6 (c 0.4, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 7.37–7.27 (m, 5 H), 4.50 (s, 2 H), 3.88 (dd, J = 9.5, 1.4 Hz, 1 H), 3.71 (dd, J = 7.7, 1.4 Hz, 1 H), 3.58–3.52 (m, 1 H), 3.39 (dd, J = 9.5, 7.7 Hz, 1 H), 2.95 (dd, J = 6.2, 4.9 Hz, 1 H), 2.05–1.87 (m, 4 H), 1.83–1.69 (m, 5 H), 1.61–1.53 (m, 2 H), 1.25 (s, 3 H), 1.11 (s, 3 H), 0.91 (d, J = 6.8 Hz, 3 H), 0.87 (s, 12 H), 0.07 (s, 6 H). ¹³C NMR (75 MHz, CDCl₃): δ = 138.7, 128.3, 127.6, 127.4, 88.0, 84.8, 78.5, 73.8, 73.3, 62.5, 60.7, 60.3, 37.5, 37.0, 34.9, 33.9, 32.3, 27.8, 26.1, 21.6, 18.3, 17.7, 16.9, –3.6, –5.0 ppm. IR (neat): ν_max = 3447, 2956, 2857, 1471, 1250. 1095, 834 cm^–1. HRMS (ESI): m/z calcd for C₃₀H₅₂NaO₅Si [M + Na]⁺: 543.3482; found: 543.3484. (S)-1-[(2R,5S)-5-{(R)-2-hydroxy-2-[(2S,5R)-2-methyl-5-(prop-1-en-2-yl)tetrahydrofuran-2-yl]ethyl}-5-isopropyl-2-methyltetrahydrofuran-2-yl]but-3-en-1-ol (10) Colorless liquid; yield 79%. R_f = 0.5 (20% EtOAc/hexane); [α]_D ²⁵ – 5.7 (c 0.2, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 5.96 (ddt, J = 17.0, 10.1, 6.8 Hz, 1 H), 5.17–5.02 (m, 2 H), 4.99 (s, 1 H), 4.79 (s, 1 H), 4.30 (dd, J = 9.9, 5.7 Hz, 1 H), 3.93 (d, J = 9.5 Hz, 1 H), 3.66 (dd, J = 9.9, 2.7 Hz, 1 H), 2.36–2.09 (m, 5 H), 2.01 (ddd, J = 17.2, 7.7, 3.4 Hz, 3 H), 1.84–1.72 (m, 2 H), 1.71 (s, 3 H), 1.44 (dt, J = 12.4, 6.6 Hz, 3 H), 1.16 (s, 3 H), 1.14 (s, 3 H), 1.01 (d, J = 6.7 Hz, 3 H), 0.86 (d, J = 7.0 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 145.8, 136.6, 116.3, 110.5, 88.7, 87.8, 85.9, 84.0, 75.3, 72.7, 37.2, 37.0, 32.2, 31.8, 31.4, 30.7, 29.0, 24.4, 23.4, 18.9, 18.0, 17.5 ppm. IR (neat): ν_max = 3470, 2975, 2936, 1472, 1153, 973 cm^–1. HRMS (ESI): m/z calcd for C₂₂H₃₈NaO₄ [M + Na]⁺: 389.2668; found: 389.2665.